Thrombectomy system, and method for extracting from thrombus region thrombus in blood vessel of patient

Abstract

To provide an operable system taking a thrombus from a blood vessel.SOLUTION: A system has a suction funnel (1), a suction catheter (2), a delivery catheter (3), a clot capture element (4), and a microcatheter (5). They are arranged coaxially mutually movably. The delivery catheter (3) progresses to a thrombus site in the blood vessel. The suction catheter (2) gives a suction force to the expandable suction funnel (1) at its end. The clot capture element (4) draws the clot captured in the suction funnel (1) into the suction funnel (1). The microcatheter (5) delivers the clot capture element (4) to a thrombus site.SELECTED DRAWING: Figure 5

Description

[Technical Field]

[0001] The present invention relates generally to the field of medical devices. In particular, the present invention relates to a thrombectomy system that allows for the removal of a thrombus at the vascular level. The present invention also relates to a method for extracting a thrombus from a thrombus site in a patient's blood vessel. In one embodiment of the present invention, the thrombectomy system includes a combination of an aspiration catheter and a clot capture element. [Background technology]

[0002] Acute ischemic stroke is a major cause of morbidity and mortality, with an annual incidence rate of 118 cases per 100,000 population and a mortality rate of 29 cases per 100,000 population per year. These figures place ischemic stroke, along with cardiovascular disease and cancer, as one of the leading causes of death in developed countries. Clinical diagnosis is necessary to establish an appropriate reperfusion (recanalization) strategy in the shortest possible time to prevent or mitigate complications associated with this disease and improve the prognosis of ischemic stroke patients. Until 2015, the treatment of choice for stroke was intravenous administration of recombinant tissue plasminogen activator (rtPA) within 4.5 hours of symptom onset. However, this drug had a narrow therapeutic window and did not always achieve recanalization. As a result, intra-arterial recanalization therapy, a form of mechanical thrombectomy, is performed using various devices (e.g., Merci®, Penumbra®). The objective of this invention is to remove thrombus by aspiration, destruction, and capture / extraction. It is considered a treatment option for patients who are not candidates for rtPA or for whom rtPA has failed. Stent retrievers (Solitaire™, Trevo®, and Revive) are making this technology more widely used, with the goal of improving the clinical results achieved with these devices.

[0003] Endovascular treatment of stroke has been available since the 1990s. The number of patients receiving the treatment has increased slowly but steadily. The main obstacle to its widespread adoption is the need for a coordinated healthcare system at various levels, meaning that patients must be able to reach a medical center capable of performing these highly complex procedures within 6-8 hours of the onset of symptoms.

[0004] The initial strategy for endovascular treatment of stroke was to locally perfuse a fibrinolytic agent via catheter directly into the clot to dissolve it. Since the 2000s, a device that appears to be more effective than intra-arterial fibrinolysis has emerged: a spiral structure (the MERCIR retrieval system) that unfolds or unfolds around the clot, facilitating its extraction.

[0005] Since 2006, a new system has become available: a large-gauge catheter designed to be advanced to the clot. This catheter (Penumbra System®) is connected to a continuous aspiration pump to aspirate the clot. [Patent Document 1] US2018 / 132876 [Patent Document 2] WO2015 / 006782 [Patent Document 3] US2017 / 119408 [Patent Document 4] WO2016 / 113047 [Non-Patent Document 1] Fennell VS, et al. "What to do fibrin rich 'tough clots' ? Comparing the Solitaire stent retriever with a novel geometic clot extractioin in an in vitro model", J NeroIntervent Surge 2018;0:1-4 doi:10 1136 / Neurintsurg 2017-013507 [Non-patent document 2] Duffy S, Farrell M, McArdle K, Thornton J, Vale D, Rainsford E, Morris L, Liebeskind DS, MacCarthy E, Gilvarry M. Novel methodology to replicate clot analogs with diverse composition in acute ischemic stroke. J Neurointerv Surg. 2017 May;9(5):486-491. [Non-patent document 3] Mokin M, Setlur Nagesh SV, Ionita CN, Mocco J, Siddiqui AH. Stent retriever thrombectomy with the Cover accessory device versus proximal protection with a balloon guide catheter: in vitro stroke model comparison. J Neurointerv Surg. 2016 Apr;8(4):413-7.

[0006] This system has evolved over the years with the goal of achieving a large diameter catheter that can be maneuvered close to the thrombus.

[0007] In 2009, stent retrievers began to be used. Their use involves crossing the thrombus with a microcatheter. An endoprosthesis is then advanced through the microcatheter. Once the distal end of the microcatheter reaches the distal portion of the thrombus, the endoprosthesis (stent retriever) is released from the sheath, self-expands, and passes through the thrombus, capturing it. It is recommended to maintain the endoprosthesis in an expanded state for several minutes to allow proper engagement of the thrombus. The expanded stent is then withdrawn, dragging the thrombus toward the catheter and removing it from the vessel. This final step is performed while applying aspiration through the catheter to reverse blood flow within the vessel, increasing the likelihood of retrieving the thrombus. Furthermore, when using stent retrievers, a guide balloon catheter (GBC) is often used. Only this GBC is advanced into the extracranial carotid artery (distant from the thrombus in the intracranial artery).

[0008] Stent retrievers have completely replaced the first-generation devices mentioned above due to their high efficacy and speed. Several prospective randomized trials have recently shown that stent retriever-assisted mechanical thrombectomy combined with standard intravenous tissue plasminogen activator (IV tPA) thrombolytic therapy is significantly superior to standard IV tPA alone for revascularization (recanalization) of acute ischemic stroke in patients with proximal large-vessel occlusion.

[0009] On the other hand, the use of stent retrievers raises a number of unresolved issues. 1. Clot fragmentation. Stent retrievers can induce clot fragmentation, leading to distal embolization in new (previously unoccluded) areas. Current aspiration catheters do not overcome this limitation because the diameter of large-bore catheters is sometimes smaller than the clot dimensions. 2. Prolonged revascularization time. Prolonged revascularization time can lead to clot fragmentation, requiring multiple recanalization attempts. 3. Navigability issues in narrow, tortuous blood vessels. 4. Over long distances, most clots must be dragged unprotected from the occlusion site to the balloon guide catheter (BGC), where they must be squeezed inward. This can result in loss of the clot or fragments breaking off. 5. Once the clot is dislodged from the occlusion site, blood flow resumes and flows against unprotected clots in the opposite direction to the retrieval movement, creating new occlusions if the clot fragments or the clot itself become detached. This is called secondary embolization. 6. Current systems for blocking blood flow (mainly balloon catheters) must be placed far upstream of the clot, rather than deep within the neurovasculature at the clot site. This means that blood circulation must be restricted in a wider brain region than just the infarct zone. This leads to the cessation of blood flow in parts of the brain not affected by the clot itself.

[0010] Furthermore, despite advances in revascularization (recanalization) tools for large-vessel occlusions manifesting as acute ischemic stroke, a large subset of clots remains recalcitrant to current strategies. Occlusions involving fibrin-rich thrombi are more difficult to recanalize and often require more attempts with this device than thrombi with a high red blood cell content (Non-Patent Document 1). For example, calcified thrombi are more difficult to remove than softer cardiogenic thrombi, whether using a stent retriever or an aspiration approach. Calcified lesions resist the contractile motion of the stent. Calcified thrombi are also difficult to remove with aspiration because they tend to be highly viscous and densely packed within the vessel. This makes it difficult to position the catheter tip within the calcified clot to maintain the vacuum required for aspiration.

[0011] Several patent applications are known in this field. For example, Patent Document 1 discloses a system for removing a blood clot from a blood vessel. The system includes a stent retriever, a catheter, a sheath (or case), and a wire. The catheter is configured to receive the stent retriever in a collapsed configuration. The stent retriever is movable relative to the catheter. The sheath is a tubular body forming a distal opening and a proximal opening. A wire is coupled to the stent retriever to deploy the stent retriever. The wire extends through the proximal and distal openings of the sheath. The stent retriever is movable relative to the sheath. The distal opening of the sheath is sized so that the stent retriever can be retracted into the sheath without substantially compressing the stent retriever.

[0012] Patent Document 2 discloses an apparatus and method for the endovascular treatment of embolism. The apparatus includes a clot treatment device and a plurality of clot engagement members. The clot treatment device includes a support member configured to extend through a delivery catheter. The plurality of clot engagement members are disposed around a distal portion of the support member. The clot engagement members are configured to penetrate clot material along an arcuate path, mechanically loosen the clot, and release embolic particles upon retraction into the delivery catheter.

[0013] Patent Document 3 discloses a clot removal device. The clot removal device includes an expandable treatment member, a delivery wire, and a blood flow restrictor. The expandable treatment member has a distal tip and a proximal end. The delivery wire has a distal end connected to the proximal end of the expandable treatment member. The blood flow restrictor is mounted along the delivery wire at a location proximal and away from the expandable treatment member. The blood flow restrictor has a body with a distal section and a proximal section. The distal section is covered, and the proximal section is uncovered. The expandable treatment member is movable relative to the blood flow restrictor and can be retracted into the distal section. Summary of the Invention [Problem to be solved by the invention]

[0014] The problem that the present invention seeks to solve is to improve the effectiveness of currently used clot capture elements, particularly stent retrievers, which are particularly effective at capturing hard clots, such as fibrin-rich clots. [Means for solving the problem]

[0015] The present invention according to a first aspect provides a thrombectomy system. The proposed thrombectomy system comprises: (A) A delivery catheter configured to be advanced through a patient's vasculature to a site of a thrombus within a blood vessel. (B) A suction catheter extending from the distal end of the suction catheter and providing suction to an expandable suction funnel. The aspiration funnel is movably disposed within the delivery catheter in a compressed, contracted state (also referred to as the "delivery state") and is at least partially external to the delivery catheter in an expanded state (also referred to as the "deployed state"). The aspiration funnel includes an impermeable covering, and the diameter of the distal end of the aspiration funnel is larger in the expanded state than in the contracted state. The aspiration funnel is configured to adapt its shape and length to the interior wall of the blood vessel. As a result, the aspiration funnel narrows and expands in length to reduce blood flow and retain thrombus within the aspiration funnel. (C) A clot capture element configured to capture a thrombus and be at least partially drawn into the aspiration funnel along with the captured thrombus. (D) A microcatheter adapted to deliver a clot capture element to the thrombus site.

[0016] In accordance with the present invention, among other things, the clot capture element is movably disposed within the microcatheter in a retracted state. Similarly, the microcatheter is movably disposed within the aspiration catheter. Furthermore, the various elements of the thrombectomy system can be moved together or separately. In one embodiment, the interconnection between these elements is via a hemostatic valve.

[0017] A thrombectomy device suitable for use for the purposes of the present invention is disclosed in US Pat. No. 5,623,999. In certain embodiments, the delivery catheter, aspiration funnel, micro-catheter, and clot capture element are longitudinally oriented, coaxially configured, and independently movable relative to one another. In certain embodiments, the suction funnel is self-expandable.

[0018] The thrombectomy system (device) of the present invention can be used in the neurovascular or peripheral vascular systems. It is particularly well-suited for navigating to the desired location and providing specific sealing where it is most needed, thus avoiding the occurrence of secondary thrombus. This design allows for the introduction of a retrieval device that functions as a clot displacing device, which removes the thrombus by drawing it into the opening of the funnel. The present approach involves guiding the thrombectomy device to a position close to the thrombus and retrieving it by suction combined with mechanical action. The aspiration funnel is a self-expandable, covered stent that is manipulated using a catheter (e.g., a guide catheter) that enables its navigation and positioning. Furthermore, the catheter is designed to maintain a vacuum from the proximal end of the catheter to the distal end near the thrombus. The vacuum is generated by an interventional device (syringe / insertion device).

[0019] The covered suction funnel can be in a contracted or expanded state, and its diameter is larger in the expanded state than in the contracted state. Furthermore, the suction funnel is designed to avoid damaging intracranial or peripheral arteries. Its design aims to adjust to the diameter of the artery, thereby restricting blood flow. Restricting blood flow is one of the most important features of the above system, preventing distal embolism. Distal embolism is a typical clinical complication when the stent retriever crosses a blood clot or during the extraction process.

[0020] In one embodiment, the expansion behavior of the suction funnel is due to the Nitinol material from which it is made. This utilizes the material's shape memory and superelastic properties. Shape memory refers to the ability to return to its original shape by deforming it and then heating the material above its "deformation temperature." Combined with its superelastic properties, Nitinol exhibits suitable properties for adapting to various diameters and shapes of blood vessels.

[0021] Furthermore, the advantages of the thrombectomy system can be summarized as follows: The suction funnel, a self-expanding stent (e.g., made of nitinol) sealed with a polymeric film, expands and conforms to the size of the blood vessel upon deployment. Advantageously, the large opening of the funnel, together with the clot capture element, allows the entire thrombus to be aspirated without fragmenting it, ensuring complete placement during the removal procedure. Clot loss is also prevented. This occurs due to the long distance from the occlusion site to the exit and the large size of the clot (which makes it difficult to capture by the clot capture element). This system can limit blood flow within the vessel, increasing the suction power of the system and further reducing clinical complications (mainly distal embolism). Another important feature of this system is that it stops blood flow directly at the thrombus site rather than at the carotid artery level, thereby affecting only a specific arterial branch rather than the entire cerebral hemisphere, improving the safety of the overall procedure. In summary, the thrombectomy system of the present invention offers clear advantages over other commercially available or planned devices.

[0022] A clot capture element, as used herein, is a device that interacts with a clot to capture the clot and retrieve it from the bloodstream. Clot capture elements according to this definition include, but are not limited to, those listed in FIG. 32.

[0023] In certain embodiments, the clot capture element is a stent retriever device. Specifically, the stent retriever device comprises a closed cell and a continuous scaffold. An example of the latter is the Solitaire™ revascularization device or TrevoStentriever™.

[0024] In one embodiment, the suction funnel includes a segment defining a distal end and a proximal end and is formed by a mesh structure consisting of multiple sets of helical filaments (or wires). The multiple sets of helical filaments rotate in opposite directions and are intertwined. They may be the same or different. The mesh structure includes a first tubular section and a second tubular section. The first tubular section has a uniform diameter. The second tubular section is adjacent to the first tubular section and has a diameter smaller than that of the first tubular section. Hereinafter, the terms "first tubular section" and "second tubular section" will be abbreviated to "first section" and "second section," respectively (i.e., the word "tubular" is omitted).

[0025] The braid structure of the first section has helical filaments with a braid angle (β). The braid angle (β) provides a higher outward radial force (i.e., pressure) than the second section. As a result, the first section better apposes or overlaps the inner wall of the blood vessel. The first section includes a closed loop at its distal end, which acts as a spring. As a result, the radial force at both ends of the first section is higher than that at the middle section.

[0026] The linear shape of the first section of the suction funnel creates a space to accommodate the aspirated thrombus. The first section is adaptable to the shape of the blood vessel, and its outer surface overlaps the inner wall of the blood vessel.

[0027] Specifically, the second section includes two subsections: a first subsection and a second subsection. The first subsection has a frustoconical (i.e., funnel-shaped) shape and includes a varying braid angle (α) between its proximal and distal ends to maintain the frustoconical shape and reduce blood flow toward the proximal end during thrombus removal. The second subsection has a tubular, uniform diameter and provides connection to an aspiration catheter.

[0028] The device of the present invention is manufactured in a variety of sizes. In one embodiment, the first section is longer than the second section. In one embodiment, the first section has a length in the range of 4-40 mm and an outer diameter in the range of 3.5-6 mm. The second sub-section has a length in the range of 1-10 mm and an outer diameter in the range of 1-2 mm. The braid angle (α) of the first sub-section is between 15-45 degrees relative to the longitudinal axis of the device. This angle allows for greater radial force to be generated, stopping blood flow. The device is compressed while sealing the vessel.

[0029] In another embodiment, the impermeable covering of the suction funnel comprises a polymer such as silicone or polyurethane.

[0030] The spiral filaments of the braided structure are made of metal, metal alloy, especially Nitinol or Nitinol / Platinum composites, such as Niti#1-DFTR (Drawn Filled Tube), where the platinum content is between 10-40%, especially 20% Platinum (Niti#1-DFTR-20%Pt). The spiral filaments are aligned longitudinally as the suction funnel narrows and lengthens.

[0031] In one embodiment, the helical filaments comprise 12-48 filaments, in particular 18-24 filaments, with a cross section in the range of 40-60 μm, in particular 50 μm, and the braid angle (β) of the helical filaments relative to the longitudinal axis of the suction funnel is in the range of 50-65° in the first section and in the range of 15-50° in the second subsection.

[0032] The aspiration funnel includes or is attached to a sensor that provides information. An example of such a sensor is an optical sensor that provides information about whether the aspiration funnel is in a retracted or expanded configuration within the delivery catheter 3. The sensor may also provide information about whether the aspiration funnel is sufficiently expanded, the presence or absence of a thrombus, the composition of the thrombus, the position of the aspiration funnel relative to the blood vessel, etc. Alternatively, the sensor may include a piezoelectric sensor that provides information about the radial forces at various sections or subsections of the aspiration funnel. The sensor may also provide information to distinguish between a clot occlusion and intracranial atherosclerosis.

[0033] Preferably, the aspiration funnel includes a radiopaque marker at its distal end or at other strategic points on the meshwork, allowing the physician to know the exact location of the aspiration funnel while using fluoroscopy.

[0034] Another aspect of the present invention relates to a method for extracting a thrombus from a thrombus site in a blood vessel of a patient, the method comprising the following steps (A)-(J): (A) Advancing the delivery catheter through the vasculature toward the thrombus site. (B) Positioning the distal end of the delivery catheter proximal to the thrombus in the blood vessel. (C) Advancing the aspiration catheter within the delivery catheter, with the aspiration funnel extending distally from the aspiration catheter. (D) The aspiration catheter and delivery catheter are moved relative to each other, positioning the aspiration funnel outside the delivery catheter and proximal to the clot. (E) Expanding the suction funnel to contact the inner wall of the blood vessel, thereby reducing blood flow through the suction funnel. (F) Advancing the clot capture element distally through the aspiration funnel toward the clot. (G) Deploying the clot capture element to capture the clot. (H) Moving the clot capture element and clot proximally towards the aspiration funnel. (I) applying suction to the aspiration funnel via the aspiration catheter, thereby aspirating the thrombus at least partially into the aspiration funnel; (J) The suction funnel and thrombus are moved proximally within the vasculature. The suction funnel adapts its shape and length to the surrounding vessels by narrowing and lengthening to retain the thrombus within the suction funnel.

[0035] The steps of the proposed method can be performed in any order, in particular step (I) may be performed before or after step (J).

[0036] Optionally, the method may include (X) advancing a microcatheter into the aspiration catheter, where the clot capture element is disposed within the microcatheter. The method may further include (Y) moving the microcatheter and the clot capture element relative to each other, whereby the clot capture element is disposed outside the microcatheter. The method may further include (Z) expanding the clot capture device.

[0037] In one embodiment, step (G) may cause the clot capture element to be self-expanding. In one embodiment, step (X) may include advancing the distal end of the microcatheter through the thrombus. Optionally, the method may also move the clot capture element proximally at least partially within the aspiration funnel. In one embodiment, step (E) includes allowing the suction funnel to self-expand.

[0038] In one embodiment, the suction funnel comprises a network of at least two sets (hereinafter "sets") of intertwined helical filaments, each rotating in a counter-rotating direction. The method further comprises moving the two sets of helical filaments into a more longitudinally aligned position as the suction funnel lengthens and narrows.

[0039] Another aspect of the present invention relates to a method for extracting a thrombus from a thrombus site in a blood vessel of a patient, the method comprising the following steps (A1)-(I1): (A1) Advancing the clot capture element distally through the vasculature toward the site of the thrombus, particularly allowing the clot capture element to self-expand toward the site of the thrombus. (B1) Advancing the delivery catheter through the vasculature toward the thrombus site. (C1) Positioning the distal end of the delivery catheter proximal to the thrombus in the blood vessel. (D1) Advancing an aspiration catheter within the delivery catheter, with the aspiration funnel extending distally from the aspiration catheter. (E1) Moving the aspiration catheter and delivery catheter relative to each other, positioning the aspiration funnel outside the delivery catheter and proximal to the thrombus. (F1) Expanding the suction funnel to contact the inner wall of the blood vessel, thereby reducing blood flow through the suction funnel. (G1) Moving the clot capture element and clot proximally towards the aspiration funnel. (H1) Applying suction to the aspiration funnel via the aspiration catheter, thereby aspirating the thrombus at least partially into the aspiration funnel. (I1) The suction funnel and thrombus are moved proximally within the vasculature. The suction funnel adapts its shape and length to the surrounding vessels by narrowing and lengthening to retain the thrombus within the suction funnel.

[0040] Step (A1) uses the clot capture element as an anchoring element, thus allowing pushability / steerability of the delivery catheter. [Brief explanation of the drawings]

[0041] [Figure 1] 1 illustrates schematically various compartments included in an aspiration funnel for extracting thrombus from a blood vessel, according to an embodiment of the present invention. [Figure 2]They are contained in different compartments of the suction funnel, with the mesh structure in the first compartment being coarser than in the second compartment. [Figure 3] 1 shows a schematic diagram of some of the main specifications of the suction funnel. [Figure 4] 1 is a graph showing the ideal pressure (P) versus diameter (D) relationship for a suction funnel. [Figure 5] FIG. 1 is a block diagram of a thrombectomy system of the present invention. [Figure 6] 1A-1C are diagrams illustrating a first step in a method for extracting a thrombus from a thrombus site in a patient's blood vessel using the thrombectomy system of the present invention. [Figure 7] FIG. 2 shows the second step of the method. [Figure 8] FIG. 10 shows the third step of the method. [Figure 9] FIG. 10 shows the fourth step of the method. [Figure 10] A diagram showing the fifth step of the method. [Figure 11] A diagram showing the sixth step of the method. [Figure 12] A diagram showing the seventh step of the method. [Figure 13] A diagram showing the eighth step of the method. [Figure 14] Diagram showing a model of the thrombectomy system. [Figure 15] 1 shows the revascularization rate after one attempt in various models using soft red clots. [Figure 16] 1 shows the revascularization rate after three attempts in various models using soft red clots. [Figure 17] Figure 1 shows the revascularization rate after a single attempt in various models using fibrin-rich clots. [Figure 18] Figure 1 shows the revascularization rate after three attempts in various models using fibrin-rich clots. [Figure 19]1. A diagram comparing the recanalization rates after one trial and three trials for the combinations (ANA+SR) and (BGC+SR) in an in vitro experiment (50 samples) and an in vivo experiment (Example 2). The absolute increase in the recanalization rate for (ANA+SR) compared with that for (BGC+SR) was similar in both experiments. [Figure 20] FIG. 1 illustrates an automated thrombectomy device (ANCD) according to one embodiment of the present invention. [Figure 21] Table 1 is shown. [Figure 22] Table 2 is shown. [Figure 23] Table 3 is shown. [Figure 24] Table 4 is shown. [Figure 25] Table 5 is shown. [Figure 26] Table 6-1 is shown. [Figure 27] Table 6-2 is shown. [Figure 28] Table 7 is shown. [Figure 29] Table 8 is shown. [Figure 30] Table 9 is shown. [Figure 31] Table 10 is shown. [Figure 32] A list of commercially available clot capture elements is provided. DETAILED DESCRIPTION OF THE INVENTION

[0042] 1 and 2 illustrate an embodiment of an aspiration funnel 1. The aspiration funnel 1 is included in an automated thrombectomy system / device (ANCD) of the present invention for removing a thrombus from a blood vessel. The aspiration funnel 1 includes a segment 10. The segment 10 is self-expanding, defines a distal end 11 and a proximal end 12, and is capable of adapting its contour to the surrounding vessel and transitioning from a contracted configuration to an expanded configuration. In the contracted configuration, the segment 10 resides within a delivery device, such as a delivery catheter 3. In the expanded configuration, the segment 10 extends from the delivery catheter 3 and is juxtaposed against the interior wall of the vessel to receive and retain a thrombus THR.

[0043] As shown in FIG. 2, segment 10 includes a mesh structure 13. This mesh structure 13 has two sets of counter-rotating, intertwined helical filaments. In one embodiment, mesh structure 13 is a diamond-shaped structure or a regular structure. The density of mesh structure 13 determines the elasticity of segment 10. As detailed in Table 1, the mesh angle relative to the longitudinal direction (i.e., braid angle (β)) is variable.

[0044] The helical filament can be made of metals (including metal alloys), polymers, composite materials including nitinol or nitinol / platinum, or DFTR (Drawn Filled Tube), or other materials with suitable mechanical properties.

[0045] 1 and 2, the network structure 13 defines two sections, namely, a first section 20 and a second section 30. In particular, the second section 30 further includes two subsections, namely, a first subsection 31 and a second subsection 32.

[0046] As shown in FIG. 2 , in this particular embodiment, the end of the first section 20 at the distal end 11 includes closed loops 23, which facilitate the expansion of the segment 10 after it exits the delivery catheter 3. Furthermore, these closed loops 23 function as springs or anchoring points by limiting movement between the helical filaments and increasing the outward radial force. The closed loops 23 provide a smooth distal end, reducing vessel trauma and improving the maneuverability (navigability) of the aspiration funnel 1 within the vessel. The remaining portion of the first section 20 forms a space that accommodates the thrombus THR after it is aspirated. The first section 20 is adaptable to the shape of the vessel because, due to its configuration (e.g., diameter and braid angle β), it provides a greater outward radial force than the second section 30. As a result, the segment 10 can adequately contact the inner wall of the vessel. The radial force at both ends of the first section 20 is greater than that at its middle section. This is for example due to the spring action of the closed loop 23. Alternatively, the radial force of the first section 20 may be distributed uniformly along all its generatrices.

[0047] The first sub-section 31 (i.e., the portion of the second section 30 adjacent to the first section 20) is frusto-conical or funnel-shaped. This shape allows the first sub-section 31 to withstand blood pressure without collapsing. In the illustrated embodiment, the change in braid angle (α) from the proximal to distal end of the first sub-section 31 provides radial strength to maintain the frusto-conical shape. The braid angle (α) at ​​the distal end of the first sub-section 31, in conjunction with the closed loop 23, maintains the first section 20 in an open position and creates space for thrombus removal. The covering of the first sub-section 31 traps thrombus, stops blood flow during thrombus removal, and protects the trapped thrombus during retraction of the segment 10 into the delivery catheter 3. The first sub-section 31 is the transition from the larger diameter of the first section 20 to the smaller diameter of the second sub-section 32. The second subcompartment 32 is for connection to the suction catheter 2 (FIG. 5) or downstream tubing.

[0048] The second subsection 32 (i.e., the portion of the second section 30 adjacent the proximal end 12) is a tubular body of uniform diameter and provides connection to the suction catheter 2. In one embodiment, the suction catheter 2 is a braided catheter covered with an outer jacket and lined with PTFE. The braid and liner of the suction catheter 2 extend distally from the outer jacket. A layer of polymeric material is placed around the protruding braid and liner, and a mandrel is placed within the braid and liner. The second subsection 32 of the segment 10 is then placed on top of this layer of polymeric material. Alternatively, another layer of polymeric material may be placed on top of the meshwork of the second subsection 32. The outer layer of polymeric material is then melted, allowing the polymer to flow through the pores (cells) of the meshwork 13, and the mandrel is removed, leaving a smooth surface throughout the suction catheter 2. This attachment approach adds structure and rigidity to the attachment section of the suction catheter 2. For this reason, the attachment section should be kept as short as possible to avoid compromising the integrity of the attachment of the segment 10 to the suction catheter 2.

[0049] Other techniques can be used to connect the segment 10 to the suction catheter 2. For example, in another embodiment, if the suction catheter 2 is a metal downstream tube, the braiding 13 of the second sub-section 32 is welded to a nitinol ring, which is welded directly to the downstream tube. Alternatively, a stainless steel ring can be glued to the braiding 13 of the second sub-section 32, and then the stainless steel ring can be welded to the downstream tube. Another option is to braid the segment 10 directly on a perforated ring, so that the filament passes through the holes.

[0050] When segment 10 is compressed within delivery catheter 3, segment 10 stretches, moving the helical filaments into longitudinal alignment, reducing the spring effect and facilitating movement of segment 10 within delivery catheter 3. This is done by reducing frictional effects and increasing pushability, which is related to the maneuverability of segment 10 within the artery.

[0051] The mesh angle or braid angle (β) allows the mesh 13 to conform to the curvature of the blood vessel, avoiding kinking (or buckling) and creating free space within the mesh to avoid obstructing the suction of thrombus.

[0052] Referring to Figure 3, some of the main specifications of the suction funnel 1 according to one embodiment are shown. Table 1 shows the main specifications of the suction funnel 1. Table 2 shows the measurement methods used to calculate these parameters.

[0053] Table 1 shows parameters for a specific embodiment. In one embodiment, the parameters of the suction funnel 1 are shown in Table 1 (Big Ref.) for a large vessel, e.g., 4.5 mm in diameter. An example of a large vessel is the last part of the carotid artery or the carotid siphon. In another embodiment, the parameters of the suction funnel 1 are shown in Table 1 (Small Ref.) for a small vessel, e.g., 2.5 mm in diameter. An example of a small vessel is the internal carotid artery (ICA) or the middle cerebral artery (MCA).

[0054] Table 2 shows the measurement methods used to calculate the various parameters. As previously mentioned, the aspiration funnel 1 has two states: a contracted state and an expanded (deployed) state. In the contracted state, the aspiration funnel 1 is within the delivery catheter 3 while approaching the thrombus site. In the expanded (deployed) state, the aspiration funnel 1 is in no interaction with the delivery catheter 3 or the blood vessel. The parameters specified herein relate to the device of the present invention in its natural (relaxed) or expanded configuration.

[0055] The segment 10 includes a radiopaque marker at its distal end 11 or at other predetermined points within the meshwork 13. Examples of radiopaque materials include platinum, tungsten, barium derivatives, gold, and iridium. This allows the physician to determine the exact location of the aspiration funnel 1 using a fluoroscope. The radiopaque material can be deposited on the helical filament after manufacture, or if there is a coating on the aspiration funnel 1, the radiopaque material can be dispersed on the surface of the coating. An alternative means for imparting radiopacity to the segment 10 is to use opacity-grade helical filaments made of different materials (e.g., nitinol and platinum). In certain embodiments, a nitinol wire with a platinum core is used. Similarly, the delivery catheter 3 can also include a radiopaque marker.

[0056] Additionally, the segment 10 includes a coating. This coating may cover only the first section 20 or may cover the entire segment 10. In the embodiment of FIGS. 1 and 2, the coating extends from the closed loop 23 to the second subsection 32, although not shown. In one embodiment, the coating is also applied to the attachment of the segment 10 to the aspiration catheter 2 by immersing the segment 10 in a liquid polymer and allowing the polymer to solidify. Optionally, a mandrel may be placed inside the mesh structure 13 of the segment 10 when immersing the segment 10 in the polymer coating material. Alternatively, the coating material may be sprayed onto the mesh structure 13. In another alternative embodiment, the coating may be applied before attaching the segment 10 to the aspiration catheter 2. In this embodiment, the coating does not extend to the proximal end 12 of the second subsection 32, but there are uncoated spaces between the helical filaments, which may be left intact for assembly with the aspiration catheter 2.

[0057] The coating prevents damage to the artery and prevents direct contact between the artery and the helical filament. Additionally, the coating provides a watertight compartment into which the thrombus THR can be drawn and protected during thrombectomy. In one embodiment, to apply the coating, the mesh structure 13 may be attached to the delivery catheter 3 and then the coating may be applied.

[0058] An internal or external glaze can also be applied to the coating to improve its properties. By applying a hydrophilic or hydrophobic coating to the exterior surface of segment 10, segment 10 can be more easily moved through delivery catheter 3 and the blood vessel due to a reduced coefficient of friction. Similarly, applying this treatment to the interior surface of segment 10 can also achieve an adhesive effect that will hold thrombus THR in place once it enters the interior.

[0059] The coating is made of a resilient material. In one embodiment, the coating of the suction funnel 1 is silicone. Alternatively, polyurethane or other types of plastic materials can be used. A mixture of polyurethane and silicone can also be used.

[0060] To achieve the dual behavior of the coating (smooth outer surface of the segment 10 and sticky or rough inner surface), the coating can be treated by adding the above-mentioned materials, or the structure of the network 13 itself can have such a structural feature.

[0061] The coating may have holes to prevent collapse of the segments 10. The holes may be formed by drilling holes in the coating after it has been applied.

[0062] The dimensions of the segment 10 depend on the dimensions of the blood vessel. The segment 10 is used to capture thrombus THR within the blood vessel. The dimensions of the subsections of the segment 10 and the braid angle of the mesh structure provide a weak radial outward force when the segment 10 is compressed and collapsed within the delivery catheter 3, and a sufficient radial outward force when expanded, helping to prevent collapse due to blood pressure. Figure 4 shows a possible work curve for one embodiment of the segment 10. The Y-axis represents the pressure (mmHg) of the segment 10, and the X-axis represents the arterial diameter (mm). The horizontal dotted line indicates the blood pressure limit. In one embodiment, the range of arterial diameters in which the suction funnel 1 of the present invention can be used is 2-5 mm. The segment 10 is designed to operate in the standard range of 2-5 mm, expand without obstruction by the artery, and handle blood pressures in excess of 200 mmHg. As shown in Figure 4, in this particular embodiment, the segment 10 is not intended to be compressed to a diameter less than 2 mm. Compression of the segments 10 within the delivery catheter 3 may result in a radially outward force large enough to prevent advancement of the aspiration funnel 1 within the delivery catheter 3 .

[0063] Some embodiments of the present invention are automated and can be used in traditional (hospital) and modern (nursing home, assisted care facility) environments. This automated device will enable widespread deployment and use of ANCDs, allowing for rapid removal of blood clots and significant improvement in patient conditions. For example, it will enable the restoration of blood flow to critical areas of the brain in a very short time. An example of such an automated device is disclosed in U.S. Patent No. 5,629,999.

[0064] During use, segment 10 (part of aspiration funnel 1) and its attached aspiration catheter 2 are advanced through delivery catheter 3 to the site of a thrombus within a patient's blood vessel. During advancement of delivery catheter 3, segment 10 is in a delivery state. In this delivery state, first and second sets of helical filaments form a distally directed first angle relative to each other. As segment 10 exits delivery catheter 3, it begins self-expanding to the deployed state. In embodiments where mesh structure 13 forms a closed loop 23 at the distal end of segment 10, the spring action of closed loop 23 of helical filaments helps expand first section 20 into apposition with the blood vessel adjacent the thrombus site. In the deployed state, first and second sets of helical filaments form a distally directed second angle. The second angle is greater than the first angle. That is, the helical filaments are less longitudinally aligned in the deployed state than in the delivery state. The first sub-compartment 31 self-expands into a frusto-conical or funnel-shaped configuration, and the distal end of the first sub-compartment 31 helps to hold the proximal end of the first section 20 in the deployed state.

[0065] The coating on the outside of the first sub-compartment 31 and the first compartment 20 reduces blood flow to the thrombus site. Appropriately placed holes through the coating allow a small amount of blood to pass through the suction funnel 1, preventing collapse of the first sub-compartment 31. This collapse can be caused by blood pressure or a pressure difference between blood pressure (external) and an applied vacuum (internal). Once blood flow is reduced, suction is applied through the catheter 2 to the interior space of the first sub-compartment 31 and the first compartment 20 to aspirate the thrombus THR into the first compartment 20. The suction funnel 1, with the thrombus THR trapped inside, is then removed from the patient. In the trapping configuration (i.e., with the thrombus THR inside), the first and second sets of helical filaments form a third angle pointing distally. The third angle is less than the second angle (i.e., the helical filaments are more longitudinally aligned). This is because the suction funnel 1 becomes longer and assumes a smaller diameter shape.

[0066] Referring to Figure 5, a schematic diagram of the expanded state of the proposed ANCD is shown. This particular embodiment includes an aspiration funnel 1, an aspiration catheter 2 connected to the aspiration funnel 1, a delivery catheter 3, a clot capture element 4, and a microcatheter 5. Detail A shows a schematic diagram of the aspiration catheter 7. The aspiration catheter 7 includes the aspiration funnel 1 and the aspiration catheter 2.

[0067] Figures 6-13 show steps in a method for extracting a thrombus THR from a thrombus site in a patient's blood vessel using an ANCD of the present invention. First, a delivery catheter 3 including an aspiration catheter 7 with an expandable tip (hereinafter simply referred to as the "aspiration catheter 7") is advanced into the internal carotid artery over a guidewire 6 and a microcatheter 5 (Figure 6). Once the delivery catheter 3 reaches a predetermined position (Figure 7), the delivery catheter 3 is withdrawn, opening the opening of the aspiration catheter 7 (Figure 8). The aspiration funnel 1 self-expands to the diameter of the blood vessel, and blood flow through the artery is stopped (i.e., blocked or partially reduced). Once the opening of the aspiration funnel 1 is opened, the microcatheter 5 is advanced into the thrombus THR (Figure 9). Next, the microcatheter 5 is withdrawn, deploying the clot capture element 4 and capturing the clot (Figure 10). The clot capture element 4 drags the clot into the opening of the aspiration funnel 1. Meanwhile, suction force is applied to the suction catheter 2 by a syringe to aspirate the clot (Figure 11). Finally, the clot engages the suction funnel 1 (Figure 12) and the system is removed (Figure 13).

[0068] Some specific examples are detailed below. In the following examples, the combination of the delivery catheter 3 and the aspiration catheter 7 is referred to as the ANA device. The proposed ANCD is therefore comprised of the ANA device, the clot capture element 4, and the microcatheter 5.

[0069] Example 1: In Vitro Assay 1. Purpose of the experiment The purpose of this experiment was to evaluate the performance of the ANA device included in the ANCD. The ANA device is a catheter system consisting of a delivery catheter 3 and an aspiration catheter 7. The aspiration catheter 7 is constructed using a silicone-covered DFT (nitinol / platinum) braided stent, as defined in Table 3. Performance was evaluated in an in vitro 3D simulation model (i.e., a cerebrovascular model of the intracranial circulation) that mimics the physiological blood flow, pressure, and vascular anatomy of the carotid artery and brain, including an occlusive ex vivo clot analog. Specifically, the purpose of this experiment is to evaluate the effectiveness of an ANA device in combination with a clot capture element such as a stent retriever (SR) in terms of revascularization (recanalization) rate and clot embolization rate.

[0070] 2. Materials and Methods 2.1 Sample The ANA devices used in the survey / experiment are as follows (Table 4): Commercially available devices are listed in Table 5. 2.2 Methodology This experiment was conducted in the animal facility of the Institut de Recerca de Valid'Hebron (VHIR) in Barcelona, ​​Spain. A mechanical thrombectomy device combining an ANA device with a stent retriever (Solitaire) and commercially available devices (Solumbra-like with a distal access catheter and Solitaire with a balloon guide catheter) were used to simulate a model cerebral vascular occlusion (containing a clot simulant). Furthermore, the performance of the ANA device, including its maneuverability and compatibility with various stent retrievers, was evaluated in the presence and absence of a clot. The procedure was followed by low-resolution fluoroscopy, assisted by a trained technician. The cerebral vasculature model system consists of a physiologically relevant simulated circulatory flow loop with a replica of a human blood vessel.

[0071] Blood vessel replica A three-dimensional in vitro model of intracranial circulation was used as a vascular replica. Two models of vascular replicas were used.

[0072] 1. Vascular Model Jacobs Institute: This model (manufactured by the Jacobs Institute) was designed based on patient vascular anatomy using CT-A imaging (50 patients) and then 3D printed. The model closely resembles human intracranial vasculature in terms of curvature, diameter, and length. The vascular model consists of an internal carotid artery segment and its branches (M1-M4 segments), bilateral A1 anterior cerebral artery segments connected to a single anterior cerebral artery, and a single posterior passage artery (right side). This allows for a nearly complete circle of the artery of Willis. Additionally, the model includes a representative access vasculature, compressing the aortic arch, common carotid artery, and cervical internal carotid artery. The tortuosity levels of the various segments of the vascular replica range from moderate to severe, creating a complete model with a tortuosity index of 7.084, compared with the mean tortuosity index of 4.752 and 2.332 for the intracranial and access vasculature, respectively.

[0073] 2. Vascular Model UMASS (University of Massachusetts Medical School): A vascular replica of the entire Willis artery circle with an ICA siphon of varying curvature, diameter, and length was selected and fabricated using a small-batch manufacturing process based on data from magnetic resonance angiograms of 20 patients. The ICA siphon with a varying curvature was selected to provide a challenging bend for endovascular access. During image post-processing, the 3D reconstruction of the vasculature was modified, and the M2 and A2 segments / portions were recombined to obtain a single output from each vascular region.

[0074] Two vessel replicas with different degrees of tortuosity were used. (1) Medium vascular model: In various compartments of the vascular replica, the average tortuosity index of the intracranial vasculature and the access vasculature was 5.831 and 0.047, respectively, and a complete model with a tortuosity index of 5.878 was constructed. (2) Severe vascular model: In various sections of the vascular replica, the average tortuosity index of the intracranial vasculature and the access vasculature was 7.067 and 7.067, respectively, and a complete model with a tortuosity index of 7.233 was constructed.

[0075] Simulated Circulation Flow Loop The model was connected to a peristaltic pump. Normal saline solution heated to 37°C was circulated through the model using the peristaltic pump. The flow rate to the complete neurovascular model was set at 370–450 mL / min, a value based on physiological flow rates. The pressure was also adjusted to 180 mmHg, a value based on physiological flow rates and the upper limit of clinically representative blood pressure. Flow and pressure sensors were placed at the inlet of the circuit after exiting the peristaltic pump, and differential pressure was calculated with a second pressure sensor placed after the vascular replica. A thermometer measured midzone fluid temperature. The intravascular device was operated under fluoroscopic guidance, and angiographic images were acquired with contrast to identify the appropriate location of the target vessel.

[0076] 2.3 Clot analogs To evaluate the efficacy of clot retrieval (revascularization / recanalization and embolization rates), we generated middle cerebral artery (MCA, M1) occlusions using soft red and fibrin-rich clots. Porcine clots were produced at VHIR. Soft red clots and fibrin-rich clots were prepared according to Non-Patent Document 3 and Non-Patent Document 2, respectively. *Soft Red Clot: 4 ml of non-anticoagulated porcine blood was mixed with 32 mg of fibrinogen from bovine plasma (F8630, Sigma-Aldrich) and 1 unit of thrombin-type bovine plasma (T4648, Sigma-Aldrich) for at least 3 minutes. The mixture was then incubated at room temperature for at least 60 minutes. *Fibrin-rich clot: Pig blood was anticoagulated using sodium citrate solution (3.2%) immediately after collection. Whole blood components were then separated using centrifugation (600g, 15 min, 5°C). Extracted plasma was mixed with red blood cells (RBCs) in a 9:1 ratio. Coagulation was initiated by the addition of calcium chloride (2.06%), and the clotted material was allowed to mature for 60 min at 37°C. The resulting clot was composed of approximately 100% fibrin. A blood clot (5x5x7mm) was injected into the flow loop to create an MCA occlusion. A total occlusion of TICI 0 was required before initiating thrombectomy.

[0077] 2.4 Procedure A Neuron Max088 guide catheter (Penumbra) was placed in the cervical ICA and a guidewire was delivered, which smoothly advanced into the target vessel. Thrombectomy (clot retrieval) *Commercially available thrombectomy device: A microcatheter was navigated across the occlusive clot over a guidewire. After withdrawing the guidewire, a stent retriever (Solitaire) for mechanical thrombectomy was deployed. During retraction of the stent retriever, continuous aspiration was performed during clot retrieval using a 60 mL syringe. *ANA and stent retriever combination: ANA was combined with a stent retriever to retrieve the clot. A stented funnel 1 was deployed proximal to the occlusion site, and a microcatheter 5 with a stent retriever (Solitaire) inside it was deployed over the guidewire through the stented funnel 1 and aspiration catheter 2 until it reached and crossed the clot. The stent retriever was deployed to capture the clot while continuous suction was applied through the ANA. The stent retriever was retracted until the entire clot was safely positioned within the stent funnel 1, and finally both devices were retrieved as a whole. In certain procedures, suction may not be applied.

[0078] 2.5. Evaluation Method (1) Evaluation of effectiveness: Revascularization (recanalization): Flow was assessed after all procedures and according to the time points of the procedures. TICI 2b and 3 were considered successful revascularization ( 1 ). TICI 0, 1, and 2a were considered as revascularization failures (0). The steps are as follows: 1. Pre-placement of the blood clot (for reference in the model vasculature) 2. Pretreatment (criteria for ischemia, clinical starting point) 3. After the first thrombectomy attempt (first revascularization attempt) 4. After the second thrombectomy attempt (if applicable) 5. After the third thrombectomy attempt (if applicable) The main endpoints considered in the efficacy evaluation were as follows: 1. Revascularization rate after the first attempt (TICI 2b-3) 2. Revascularization rate after the third attempt (TICI 2b-3)

[0079] Embolic events (ENT / EDT). Flow was assessed after all procedures and according to the time point of the procedure. The distal zone (EDT) and new zone of embolization (ENT) were evaluated. An EDT score of 0 and an ENT score of 0 indicate no embolic events. An EDT score of 1 and an ENT score of 1 indicate an embolic event. The steps are as follows: 1. Pre-placement of the blood clot (for reference in the model vasculature) 2. Pretreatment (criteria for ischemia, clinical starting point) 3. After the first thrombectomy attempt (first revascularization attempt) 4. After the second thrombectomy attempt (if applicable) 5. After the third thrombectomy attempt (if applicable) The main endpoints considered in the efficacy evaluation were as follows: 1. EDT and ENT after the first attempt (TICI 2b-3) 2. EDT and ENT after the third attempt (TICI 2b-3)

[0080] (2) Evaluation of operability: Usability was assessed after the first attempt. The following evaluation criteria were used to assess usability: 1. Operation time (s): The time required to reach the target vessel 2. Usability / Flexibility: Ratio of operation time to score Here, the score is an evaluation point of the ability to push the device into the target blood vessel and the controllability of the device in the vicinity.

[0081] 2.6 Experimental Design Table 6 shows the experiments performed for each group and condition for various evaluations. The maximum number of thrombectomy attempts was limited to three. Table 6-1: Availability of commercially available devices Table 6-2: Efficacy of ANA in combination with stent retrievers In the table, "fiber-rich" means "fibrin-rich" and "soft red" means "soft and red."

[0082] 2.8 Data Analysis Revascularization and embolization values ​​were expressed as percentages. Group means were calculated. Performance scores were analyzed qualitatively, and group means and SDs were calculated. Consistency data were assessed qualitatively. Statistical analysis of revascularization, embolization, and operability values ​​was performed using Excel. T-tests were applied to compare the means of two groups, and a probability value of p<0.05 was considered statistically significant.

[0083] 3. Results (% display) Table 7 (intrac = brain) BGC stands for balloon guiding catheter, and DAC stands for distal access catheter. For soft red clots, the results of combining ANA with Solitaire were comparable to or better than those of combining Solitaire with BGC or DAC (Figure 15). Similar results were observed for all three models in the first and third trials (Figure 16). For fibrin-rich clots, the results of combining ANA with Solitaire were consistently superior to those of combining Solitaire with BGC or DAC (Figure 17). Similar results were observed in all three models, between the first and third trials (Figure 18). Similar results were observed with other stent retrievers (data not shown).

[0084] 4. Conclusion ANA combined with a stent retriever demonstrated superior and significant recanalization rates in fewer attempts compared with other commonly used device combinations, such as BGC and DAC combined with a stent retriever, especially in fibrin-rich clots. Extrapolating these results to clinical practice, acute ischemic stroke with large vessel occlusion and clinical mismatch is better treated directly with ANA combined with a stent retriever, which obviates the need for salvage therapy.

[0085] Example 2: In vivo assay: Long-term evaluation of the performance and safety of ANA in combination with a clot-trapping element (e.g., a stent retriever (SR)) in a porcine clot model. 1. Introduction and Purpose Endovascular therapy (EVT) is recognized as the most effective treatment for large vessel occlusion (LVO) stroke. It has been demonstrated that achieving the highest degree of recanalization in the shortest time with the fewest attempts correlates with improved clinical outcomes. While highly effective, complete recanalization is not achieved in approximately 20% of treated patients. To improve patient outcomes, various devices and combinations have been developed to increase the rate of complete recanalization on the first attempt. The development of such devices involves preclinical testing in phantom and animal models. Phantom models mimic the human anatomy of the cerebral vasculature. Animal models allow for the evaluation of devices in relation to vascular injury. Because each simulation model has its own unique characteristics, it is recommended that new devices or combinations be proven effective and safe under a variety of conditions before final evaluation in initial human trials.

[0086] The purpose of this experiment was to evaluate the preclinical efficacy and safety of ANCD combined with an assist device in a porcine model on days 3 and 30 after three trials, and specifically to confirm that the use of a self-expanding funnel was not associated with higher vascular injury compared with commonly used devices. The experimental design was as follows: *Day 0 acute performance assessment of revascularization (clot retrieval) efficacy. *Angiographic and histological evaluation at days 3 and 30 to assess local and end-organ tissue response.

[0087] 2. Method The ANA device in this case includes a delivery catheter 3 and an expandable tip aspiration catheter 7 . The aspiration catheter 7 is composed of a braided metal structure overlaid with a highly flexible polymer. Its purpose is to locally restrict blood flow during intervention. The aspiration catheter 7 includes a self-expandable funnel 1 that, upon exiting the sheath / case, expands to the diameter of the vessel, adapting to the vessel's shape and restricting blood flow. When combined with a retrieval device, the aspiration catheter 7 can provide effective suction, functioning as a complementary mechanism. The aspiration funnel 1 is designed to be flexible enough to accommodate the curvature of the neurovascular system. The aspiration funnel 1 is composed of a radiopaque braid and a polymer film.

[0088] Delivery Catheter 3 is the outermost catheter in the ANA device and has a hydrophilic coating to reduce friction during navigation and use to reach the target vessel, and a radiopaque marker at the distal tip for angiographic visualization. The material used allows for increased flexibility at the tip and sufficient rigidity and pushability in the proximal section.

[0089] Animal models All animals were quarantined and housed at CBSET (Lexington, Massachusetts, USA). This facility is accredited by the Association for Accreditation of Laboratory Animal Care of the United States Department of Agriculture and operates under conditions specified by USDA guidelines. Standard veterinary care was provided during quarantine. This care included physical examinations and clinical pathology to determine health status before exposure to experiments. A species-appropriate, balanced diet was provided daily to all animals, with water available ad libitum.

[0090] Eleven pigs (female or castrated male Yorkshire pigs, weighing 39-50 kg) were used in this experiment. This pig model was selected as the experimental species for this experiment because the size and anatomy of the vasculature are clinically relevant for testing catheter-based medical devices for the treatment of vascular disease. Furthermore, pigs are an established animal model for vascular experiments and are generally accepted as a scientific standard.

[0091] The animals were anesthetized, intubated, and catheterized with an IV catheter to administer supportive IV fluids and medications. Surgical procedures were performed under aseptic conditions. Physiological parameters were monitored throughout the entire procedure. The femoral artery was accessed via a cut-down approach. An A9F introducer sheath was advanced into the artery, and heparin (150 U / kg IV) was administered to extend the activated clotting time (ACT) to approximately 200-350 seconds. ACT levels were monitored every 45 minutes throughout the entire procedure. Additional heparin was administered as needed to maintain the target ACT. Under fluoroscopic guidance, an 8FMach1™ guide catheter (CGC; Boston Scientific, Marlborough, MA) was advanced through the sheath / case over the guidewire into the descending aorta and target artery. Angiographic images were obtained with a contrast medium / contrast agent to identify the appropriate location for the treatment site. Angiographic analysis was performed throughout the entire procedure (baseline examination, after each attempt, and before autopsy). Parameters assessed (qualitatively and quantitatively) on angiography were vascular anatomy, target site, device monitoring, vascular status - injury, vasospasm, and blood flow (mTICI scale).

[0092] Two different recanalization strategies were attempted according to the Instructions For Use (IFU) to perform the target vessel intervention. 1. BGC + SR: balloon guide catheter (BGC: 8FrFlowGate2™ balloon guide catheter (95 cm); Stryker Neurovascular, Fremont, Canada) + stent retriever (SR: Solitaire™) 24 x 40 mm; Medtronic Neurovascular), 2.ANA+SR

[0093] The cervical and lingual arteries were used in the experiments. These arteries cover a diameter range of 2.2–5 mm for ANA+SR and 2.7–5 mm for BGC, representing the size of the target vessels in the cerebral vasculature (internal carotid artery (ICA) and middle cerebral artery (MCA)).

[0094] The ANA+SR and BGC+SR devices were positioned along the target vessels to ensure that all vascular beds were evaluated at each time point. Randomization of animals was not required in this study because each animal was evaluated with both the ANA+SR and BGC+SR devices.

[0095] To simulate a worst-case scenario, three attempts were performed for each experimental group. Three attempts is the maximum number of deployments and deflations allowed for the ANA device and the Solitaire Stent Retriever according to the IFU. Potential vascular injury (perforation, dissection, thrombosis) caused by the device and vasospasm was also assessed angiographically during the procedure.

[0096] Clot preparation and delivery Previously (24-48 hours) generated hard (high fibrin) and soft clots from autologous blood were administered into the target treatment vessels (carotid and lingual arteries). Vessel and clot consistency was randomly selected to ensure even distribution across the test and control devices. Hard clots were generated using whole blood samples (50 mL) collected in standard tubes. The samples were then centrifuged to extract 10% of the lower red blood cell layer, including the buffy layer, and the serum layer. This extracted solution was mixed and incubated for 2 hours. Soft clots were generated using porcine blood (up to 30 mL) incubated at room temperature for 2 hours. In both cases, the solid components were stored at 4°C in the same container as the control until the time of the procedure. The clots were cut into pieces appropriate for the target vessels before administration. The clot was introduced into the target area via an 8F guide catheter via a customized Luer to minimize shearing / fragmentation. Angiography was performed later to confirm vessel occlusion (TICI 0). The clot was allowed to stabilize within the vessel for 5-10 minutes before thrombectomy.

[0097] Thrombectomy Mechanical thrombectomy was performed using either ANA+SR or BGC+SR, and the ability to retrieve the clot was assessed. TICI flow (mTICI scale) and vasospasm were assessed after clot management and after each thrombectomy attempt. The intravascular device was manipulated under fluoroscopic guidance, and angiographic images were obtained to identify the proper location of the device.

[0098] In all interventions, a microcatheter (Rebar 18, Medtronic Neurovascular) was advanced over a 0.014-inch microguidewire (Synchro; Stryker) to the proximal aspect of the occlusive clot. *In intervention 1, the BGC was inflated to stop blood flow before performing thrombectomy using the SR, as per IFU and usual practice. Suction was applied through the BGC with the SR withdrawn and the microcatheter 5 in place. *In intervention 2, delivery catheter 3 was advanced near the proximal aspect of the clot, and aspiration funnel 1 was deployed proximal to the clot to locally stanch blood flow. Next, microcatheter 5 was advanced through the clot, and SR was deployed as per standard practice. At this point, microcatheter 5 was fully withdrawn, and suction force via aspiration catheter 7 was increased. The SR was then slowly withdrawn until its proximal end was inside aspiration funnel 1, and suction was initiated, gradually withdrawing the combined ANA and SR. *In all interventions, aspiration during thrombectomy was performed using a 60 cc syringe (Vaclock; Merit Medical) connected to a three-way stopcock via either the BGC (intervention 1) or aspiration catheter 7 (intervention 2). For each clot, recanalization attempts using the same strategy were repeated for two more attempts (last attempt). Angiography was performed after each attempt to assess recanalization (TICI flow) and vasospasm. The recanalization rate (TICI 3) was calculated considering the first and third TICI data.

[0099] The resulting experimental design is summarized in Table 8 below. Table 8. Experimental design: test equipment (ANA, FlowGateBGC, Solitaire), number and location of vessels, number of animals involved, evaluation time points.

[0100] histopathology Animals were euthanized after 3 and 30 days and underwent comprehensive necropsies. Treated vessels were dissected and dissected, and relevant tissues and organs were collected, fixed in 10% Neutral Buffered Formalin (NBF), paraffin-embedded, and stained with H&E (Hematoxylin and Eosin) and Verhoeff for histomorphometric evaluation. Each treated vessel was trimmed to obtain at least six cross sections (two proximal, two middle, and two distal) within the estimated treatment area. For tongue treatment, treated vessel cross sections were taken from breadloafed tongue sections, including the surrounding parenchymal tissue. Additionally, an untreated distal segment of the vessel was obtained within approximately 5 mm of the distal end of the estimated treatment area.

[0101] Histomorphometric score values ​​for predefined parameters were determined using light microscopy. These predefined parameters reflect the degree of host response / repair process to treatment in the target vessel. Histomorphometric markers included vascular injury, vessel wall compression lesions, inflammation, endothelialization, luminal fibrin / thrombus deposition, neointima formation, and exogenous fibrosis. Histologic sections of the vessels were examined for other microscopic changes, including hemorrhage, necrosis, and the type and relative amount of inflammatory cell infiltration. Representative downstream tissue sections were evaluated for treatment-related adverse events, including thrombosis, necrosis, inflammation, and the presence of embolic material. Score values ​​were calculated across all sections and levels and reported as an overall average for each vessel, with a ranking ranging from 0 (no injury) to 3 (highest injury) for all markers, except for endothelialization, which was ranked from 0 (no endothelial coverage) to 4 (complete endothelial coverage). Pathologists were blinded to the treatment matrix at the time of reading.

[0102] statistical analysis Frequency statistical analysis was obtained and comparisons were performed using a statistical package (SPSS). The methods used to evaluate the statistical significance of differences between groups were Pearson X2, Fisher's exact test for categorical variables, Student's test, and analysis of variance for continuous variables. In this example, the Mann-Whitney U test and Spearman test were used. All tests were considered statistically significant at a probability value of p<0.05.

[0103] 3.Results Angiography results A total of 26 thrombectomy interventions (13 interventions with BGC+SR and 13 interventions with ANA+SR) were performed in 11 animals. The results of this study, using the ANA device and the Flow Gate BGC device (both in combination with the Solitaire device), are shown in Table 9, which shows the recanalization rates after one and three attempts using soft and hard clots. Table 9 shows the recanalization rates after one and three attempts using ANA+SR and BGC+SR. For soft clots, the results of the ANA plus Solitaire combination were consistently superior to the results of the Solitaire plus BGC combination in both one and three trials. For hard clots, the results of ANA plus Solitaire were consistently superior to those of Solitaire plus BGC in both one and three trials.

[0104] After the first attempt, the recanalization rate (TICI3) was 69% with ANA+SR and 46% with BGC+SR. With additional attempts, recanalization rates increased in both treatment groups: 100% with ANA+SR and 77% with BGC+SR. The mean number of attempts to achieve complete recanalization tended to be fewer with ANA+SR (1.4 attempts) compared with BGC+SR (1.9 attempts).

[0105] The ANA device performed similarly to the FlowGate control in terms of compatibility between device components and ancillary devices, pushability of the catheter through the anatomy, catheter radiopacity, and device integrity after use. The ANA device performed slightly better in terms of navigability / trackability and flexibility within the vessel compared to the FlowGate BGC.

[0106] One distal embolism was observed angiographically and confirmed on day 3 in the BGC+SR group, whereas no distal thromboembolic events were observed in the ANA+SR group.

[0107] Angiography showed that three dissections occurred during the intervention: one in the ANA+SR group and two in the BGC+SR group, but none of them were related to the ANA or Solitaire device because they were observed immediately after catheterization with either the guide catheter or BGC into the target artery. The second dissection in the BGC+SR group was mild and was not associated with further complications.

[0108] Regarding occlusion, a total of seven occlusions were observed after 3 or 30 days. Two occlusions detected after 30 days (one in the ANA + SR group and one in the BGC + SR group) occurred after severe dissection. Three occlusions (one in the ANA + SR group after 3 days and two in the BGC + SR group after 3 and 30 days) were considered natural procedural complications. Two occlusions observed during angiography at 3 days (two in the BGC + SR group) were related to failure to retrieve the clot after completion of the procedure (maximum of three attempts). No vessel perforation was observed in either group. Vasospasm was commonly observed to varying degrees in both groups. This is a common observation in the porcine model, as pigs are prone to vasospasm.

[0109] Histological results A total of 24 vessels (2 of 26 vessels were discarded due to severe dissection) and associated downstream tissues were evaluated histologically. Histomorphological markers of vascular mural injury were absent or minimal and comparable between the ANA+SR and BGC+SR groups on days 3 and 30. In general, all markers (including vascular injury, vessel wall compression inflammation, thrombus, or hemorrhage) were absent or minimal, showing scores of less than or approximately 1 across both groups and time points. Endothelial coverage was lowest at day 3 (ANA+SR: 1.78 ± 1.22, BGC+SR: 2.03 ± 1.20; p = NS) but increased over time, becoming nearly fully circumferential by day 30 in both groups (ANA+SR: 3.77 ± 0.23, BGC+SR: 3.50 ± 1.07; p = NS).

[0110] Therefore, vascular injury was absent or minimal, and was comparable between the ANA+SR and BGC+SR groups on days 3 and 30, with no statistical differences. Other findings, such as inflammation, thrombosis, embolism, and necrosis in tissues downstream to the carotid artery (brachiocephalicus muscle) and lingual artery (tongue), were also absent or minimal in both groups and time points. Most scores were 0 and less than 1.

[0111] 4. Conclusion This study in a porcine clot model demonstrated that the ANA device combined with the Solitaire™ 2 has a safety profile comparable to that of a balloon guide catheter combined with the same stent retriever. Furthermore, the observed efficacy profile is similar to findings achieved in a previous preclinical study using a 3D-printed phantom (Example 1), despite differences in vessel tortuosity and experimental environment.

[0112] Histopathological analysis findings confirmed that the ANA device had no adverse effects on the arterial wall, with minimal findings comparable to those in the BGC+SR group. To characterize the safety profile in a setting simulating actual human cases, target arteries of 2.2–5 mm were selected. These diameters are smaller (thinner) than the arterial segments in which guide catheters and BGCs are typically placed. This may explain the fewer arterial dissections and occlusions observed following guide catheter / BGC manipulation before ANA / SR deployment.

[0113] The innovative design of the Aspiration Funnel 1, namely its self-expandable braided components (which adapt to the vessel and conform to the vessel wall, combined with suction and the resulting local vacuum), clearly suggests a greater risk of vascular injury than conventional endovascular devices currently used in routine neurothrombectomy. However, current research findings suggest that the design of the Aspiration Funnel 1 and the entire ANA device is atraumatic to the vasculature. This is primarily due to the balanced radial force of the Aspiration Funnel 1. This radial force, combined with the smooth silicone covering of the Aspiration Funnel, is balanced to be large enough to adapt to the vessel and allow suction, but not so large as to damage the vessel wall. Furthermore, the catheter surface and tip are smooth with a coating, facilitating navigation and preventing vascular trauma. A favorable safety profile for treated vessels has been demonstrated by histopathological and angiographic evaluations. These evaluations clearly demonstrate that vascular injury caused by the ANA device combined with SR is unrelated and similar to that of BGC+SR. The reasons for this are that histomorphometric market scores were absent or minimal, no perforations occurred, and the cases of dissection were unrelated to the ANA device but related to conventional procedures (BGC or guide catheter).

[0114] Notably, the ANA device combined with the stent retriever achieved a high complete recanalization rate with fewer attempts. Therefore, the proposed ANCD exhibits an improved efficacy profile compared with current commercially available products. The observed efficacy rate is consistent with the recanalization rate achieved in Example 1 (in vitro model). Furthermore, the fact that the BGC+SR combination demonstrated similar recanalization results in both models (phantom model and animal model) and in actual patients may indicate that the results of human clinical trials using the ANCD are consistent with the current results obtained in preclinical models.

[0115] Recent publications have indicated that not only are higher recanalization rates associated with better outcomes, but achieving the same recanalization rate with fewer attempts (ideally only one attempt) is also a predictor of improved long-term outcomes. They further indicate that currently approved and widely used thrombectomy devices and combinations achieve complete recanalization rates in the range of 40-50% on the first attempt. Novel devices, such as the proposed ANCD, may have an improved efficacy profile that can increase first- and last-attempt success rates, potentially improving short- and long-term outcomes for stroke patients undergoing endovascular therapy (EVT).

[0116] The ANA device (and thus the ANCD) induces local flow arrest in combination with complete clot ingestion into the suction funnel, preventing clot fragmentation and distal embolization. These features / functions are supported by preclinical observations in both printed in vitro phantom models (Example 1) and animal studies using soft and hard clots. While these promising results cannot be used as a predictor of similar success rates in initial human trials, they may represent the best preclinical evidence achieved at this stage. Furthermore, the results observed in this study indicate that the safety profile of the ANA+SR combination is similar to that of the commonly used BGC+SR combination.

[0117] The experiments reported were performed under good laboratory practice in an independent facility, and the results were obtained directly from official regulatory reports. The conclusions can be summarized as follows: 1. Preclinical results in a porcine clot model support the high efficacy of ANA+SR without causing clinically significant vascular injury associated with the novel funnel components. 2. The efficacy profile of this in vivo experiment is similar to that of the in vitro phantom model (Example 1, Figure 19), and the enhanced ANA device, when combined with a stent retriever that maintains a similar safety profile, is more effective than commonly used devices in mechanical thrombectomy. 3. This experiment demonstrated that the ANCD outperformed the FlowGate™ balloon guide catheter in terms of handling, positioning, pushability, and trackability. 4. No treatment-related health or clinical issues. All animals survived to the scheduled evaluation time points. Pathologists reported that the ANA device demonstrated comparable tissue reactions to the control FlowGate™ Balloon Guide Catheter device (at days 3 and 30) when both were used in combination with the Solitaire™ 2 Revascularization Device.

[0118] Example 3: Human Clinical Trial: A prospective, single-arm, multicenter study to evaluate the safety and performance of an ANA device in combination with a clot capture element (e.g., a stent retriever (SR)) in patients with acute ischemic stroke. The first patient in the next clinical trial was enrolled on September 21, 2017, and treatment is currently ongoing. 1. Introduction and Objectives As described above, the ANA device is a distal access catheter designed to assist in neurovascular procedures by facilitating the insertion and guidance of other devices (i.e., retrieval devices and intravascular catheters) and restricting blood flow at the target location. In this specific embodiment, the ANA device is a sterile, disposable intravascular device. The intravascular device consists of two coaxial catheters (delivery catheter 3 and self-expandable aspiration catheter 7) with varying stiffness sections. The aspiration catheter 7 contains a radiopaque nitinol braid (self-expandable funnel 1) covered with a continuous silicone coating that, when deployed, provides localized, temporary blood flow restriction. The delivery catheter 3 has a hydrophilic coating to reduce friction during use and a radiopaque marker at its distal end. Both catheters 1 and 7 have Luer lock hubs at their proximal ends.

[0119] The proposed study was designed to gather prospective clinical evidence comparing the ANA device with similar devices. These devices are used to guide and support a stent retriever during neurothrombectomy. This protocol was designed to utilize a patient population enrolled in a previous study of similar devices as a repeat subject. The primary endpoint was the ability of the ANA device to facilitate stent retriever deployment and neurothrombectomy in the anterior circulation. Successful reperfusion (canalization) was defined as a modified Thrombolysis in Cerebral Infraction (mTICI) score of 2b or greater in the target vessel within three or fewer ANA device attempts, without the use of rescue therapy. Follow-up at 24 hours, day 5 (+ / - 12 hours), or at the time of discharge, whichever occurs first, and 90 days would allow for documentation of the clinical outcomes and evidence of other complications throughout the neurothrombectomy procedure using the ANA for distal access. The experiment was conducted in accordance with ISO standard 14155 (Clinical investigations of medical devices in human subjects - Good clinical practice).

[0120] The purpose of this study was to evaluate the safety and performance of the ANA catheter system used as a tool to facilitate the placement of the Solitaire Stent Retriever, temporarily restricting blood flow in stroke patients undergoing neurothrombectomy for acute large vessel occlusion (LVO), and in patients presenting (to the neuroimaging laboratory) within 8 hours of symptom onset (the last time the subject appeared well).

[0121] 2. Method Primary endpoint Performance was assessed as the ability of the ANA device to facilitate stent retriever deployment and neurothrombectomy in the anterior circulation. Successful reperfusion was defined as a modified Thrombolysis in Cerebral Infarction (mTICI) score of 2b or greater in the target vessel on three or fewer ANA device attempts without the use of rescue therapy. Safety was assessed by the occurrence of any serious adverse events attributable to the device up to 90 days after the procedure, including symptomatic intracerebral hemorrhage (sICH) within 24 hours (-8 / +12 hours) after the procedure.

[0122] Secondary endpoints The secondary performance evaluation items for this study are as follows: 1. The ability of the ANA device to reach the site of a large vessel occlusion, allowing for manipulation and deployment of the stent retriever to attempt neurothrombus ablation and pass through the internal carotid bulb at least into the anterior cerebral circulation. 2. Procedural time, defined as the time from puncture to achieving mTICI ≥ 2b in <3 attempts, or, if not achieved, to final angiography. 3. Treatment time, defined as the time from the door to puncture to the first baseline angiogram to achieving an mTICI of 2b or greater in less than three attempts, or, if not achieved, to the final angiogram. 4. Neurological status. The time points for this assessment are Day 5 (+ / - 12 hours) or at time of discharge, whichever comes first, and Day 90 (+ / - 14 days), as determined by NIHSS score. 5. Modified Rankin Scale (mRS) score. The evaluation time points are Day 5 (+ / - 12 hours) or at the time of discharge, whichever comes first, and Day 90.

[0123] The secondary safety endpoints of this study were: 1. Evaluation of intracerebral hemorrhage (ICH): Symptomatic or asymptomatic intracerebral hemorrhage (ICH) at 24 hours (-8 / +12 hours) was assessed by magnetic resonance imaging (MRI) / computed tomography (CT). ICH was defined as extravascular blood within the brain or skull. ICH was considered symptomatic and identified as the primary cause of neurological deterioration if it was associated with clinical deterioration (a worsening of the National Institutes of Health Sciences score of more than 4 points) or if it led to death. This was adjudicated by an independent clinical events committee. 2. Incidence of subjects with neurological deterioration of >4 points on the NIHSS at 24 hours (-8 / +12 hours): This was assessed by an independent investigator (i.e., not involved in patient screening or thrombectomy). 3. The occurrence of embolization in previously uninvolved areas on cerebral angiogram. 4. Procedural mortality. The time point for this determination is day 5 (+ / - 12 hours) or time of discharge, whichever occurs first. 5. Occurrence of complications due to the procedure: arterial perforation in the target vessel, arterial dissection and vasospasm, and embolization in previously uninvolved areas. 6. Development of infarction in previously uninvolved vascular territories, as assessed by 24-hour imaging (MRI / CT) after the procedure.

[0124] Study site and population sample size The trial will be conducted in up to five large, comprehensive stroke centers (available 24 / 7) within the European Union. Currently, the proposed sites are in Spain, but other European countries may be added later. The stroke centers involved are: Hospital Germans Trias i Pujol, Hospital de Bellvitge, Hospital Clinic, Hospital Vall d'Hebron, Hospital las Cruces de Bilbao.

[0125] The study population is based on patients with acute ischemic stroke (AIS). Their stroke is due to occlusion of a major artery in the neurovascular system (e.g., the internal carotid artery, the M1 or M2 segment of the middle cerebral artery). Patients are either ineligible for IV alteplase (tissue-type plasminogen activator [t-PA]) or have received IV t-PA therapy without adequate recanalization, but the time from symptom onset (last time they appeared healthy) to groin puncture in the catheterization lab is less than 8 hours. A total of 125 subjects eligible for treatment with the ANA device in combination with the Solitaire Stent Retriever are expected to be enrolled. The inclusion and exclusion criteria for patient selection are detailed in the clinical trial protocol.

[0126] This study is estimated to take 5-6 months to enroll 125 subjects, recruiting 5-6 patients per month per stroke center, or 25-30 patients per month. Each patient will be committed for a 90-day + / - 2-week participation period. Analyses will include the primary performance and early secondary endpoints at patient 35 on day 5 (+ / - 12 hours) or at discharge. Interim analyses will be performed and interim study reports will be generated.

[0127] The following study populations are defined for the purposes of statistical analysis: 1. Enrolled population: defined as all subjects who gave informed consent to participate in the study. 2. Intent-To-Treat (ITT): Defined as all subjects who participate in the procedure and are enrolled in the study. 3. Modified Intention to Treat (mITT): Defined as all subjects from the ITT analysis set, excluding roll-in subjects, which are defined as the first subjects from each investigator.

[0128] Experimental procedure and evaluation Table 10 below shows the schedule of assessments recorded during baseline, intraprocedure, and periodic assessments. Periodic assessments were performed 24 hours after the procedure, on day 5 (+ / - 12 hours) or at discharge (whichever came first), and at the 90-day follow-up clinic visit. Table 10: Evaluation Schedule All thrombectomy patients who presented to participating study sites after the start of the study were tracked anonymously in a patient screening log to identify patients who were not participating in the study. The reasons for not participating in the study were recorded in the screening log.

[0129] Analysis method: Statistical analyses were performed using SAS System® version 9.4 or later. A complete statistical analysis plan was developed before performing the analyses. A full description of all derived variables used in the report was given, and statistical tables and lists were also generated. All statistical analyses were performed in a locked database following data clarification resolved through a data management process.

[0130] The primary analysis set for statistical reporting was the ITT population, and to provide unbiased results, no planned imputation of missing data was performed in the statistical analysis. However, two sensitive analyses were performed regarding missing values ​​for the primary performance endpoint. The first analysis took a conservative approach and entered failure instead of missing values. The second analysis imputed missing values ​​with the same repartition, using the pass / fail repartition reported for nonmissing values. The same statistical tests were presented in both analyses. Furthermore, the primary endpoint was reported in the mITT population.

[0131] With the exception of the primary performance endpoint, statistical tests were not performed on any of the study parameters, and only descriptive analyses were provided to fully describe the recorded parameters. The primary performance endpoint was analyzed using a binomial test, as indicated in the experimental protocol. Heterogeneity of results for the primary endpoint was assessed by comparing the success rates between sites. This was performed using a bilateral Chi-Squared test at the 5% level. Furthermore, the same analysis was performed by pooling sites from the same town. These analyses were performed only on the intention-to-treat population.

[0132] When subject 35 was discharged, on Day 5 (+ / - 12 hours) or at discharge, an interim analysis including the primary performance and early secondary endpoints was performed and an interim study report was generated.

[0133] Continuous variables will be summarized using standard quantitative statistics: number of non-missing observations, mean, standard deviation, median, quartiles, and range (minimum and maximum observations). Categorical variables are summarized using classical frequency statistics. Frequency statistics are the number of non-missing observations and the percentage per category. The percentage is calculated based on the number of non-missing observations. The number of missing observations is also determined. Where applicable, bilateral asymptotic or exact confidence intervals (Cls) for the bilateral distribution will be calculated at the 95% level (unadjusted 95% Cl). The primary and early secondary endpoints will be assessed in both the ITT and mITT populations. Other secondary endpoints will be assessed in the ITT population only. AE data will be summarized using descriptive statistics: total number of events and number of subjects with at least one of each category: AE, ADE, SAE, SADE, or device defect. Severity and causality will be displayed.

[0134] Referring to FIG. 20, another embodiment of an ANCD 600 of the present invention is shown. The ANCD 600 is capable of automated navigation through the vasculature. According to this particular example, an automated proximal device 601 provides a guidance system for deploying the thrombectomy device 600. Additionally, an imaging device 602 detects radiopaque markers included on the segment 10 and delivery catheter 3. A communication channel 603 provides a means for transmitting images to a control module 604. The control module 604 is programmed or configured to provide guidance for the deployment of the thrombectomy device 600 and the storage of data in a data storage device 605. The control module 604 may be a programmable logic controller, computer, or the like. In this embodiment, the control module 604 is guided by a computer-assisted controller 606. The communication channel 603 may be Ethernet, WiFi, Bluetooth, or the like. Control module 604 is programmed to guide a physician or technician operating thrombectomy device 600. This allows thrombectomy device 600 to be used in non-hospital settings, such as nursing homes or assisted living facilities.

[0135] By enabling thrombectomy device 600 to be used "in situ," the time required for thrombectomy is significantly reduced, resulting in a significant improvement in the patient's condition. Control can also be via a controller, such as those used in other medical devices currently in use. In another embodiment, the system can be manually controlled.

[0136] The above description relates to one embodiment of the present invention. Those skilled in the art may conceive of various modifications of the present invention, all of which are within the technical scope of the present invention. The numbers in parentheses following elements of the claims correspond to part numbers in the drawings and are provided for easier understanding of the invention and should not be used to limit the interpretation of the invention. Furthermore, even if the part numbers are the same, the part names in the specification and claims are not necessarily the same. This is for the reasons stated above. Regarding the term "or," for example, "A or B" includes the selection of "A only" or "B only," as well as "both A and B." Unless otherwise specified, the number of devices or means may be singular or plural. Note that "Bluetooth®" is a registered trademark. [Explanation of symbols]

[0137] 1: Suction funnel 2: Suction catheter 3: Delivery catheter 4: Blood clot trapping element 5: Microcatheter 6: Guide wire 7: Suction catheter 10: Segment 11: Distal end 12: Proximal end 13: Mesh structure 20: First section 30: Second section 31: First subdivision 32: Second subdivision Figure 14 Fluoroscopy Input Control Differential Control Temperature control Blood vessel replica Figure 15 First attempt: soft red clot Flexed access, moderate flexion, severe flexion Figure 16 Third attempt: soft red clot Flexed access, moderate flexion, severe flexion Figure 17 First attempt: fibrin-rich clot Flexed access, moderate flexion, severe flexion Figure 18 Third attempt: fibrin-rich clot Flexed access, moderate flexion, severe flexion Figure 19 1st attempt, 3rd attempt, 1st attempt, 3rd attempt Figure 20 600: Thrombectomy device 601: Automated Proximal Device 602: Imaging device 603: Communication channel 604: Control module 605: Data storage device 606: Computer-Aided Controller

Claims

1. In the thrombectomy system, (A) a delivery catheter (3) advanced through a patient's vasculature to the site of the thrombus within a blood vessel; (B) a suction catheter (2) having an expandable suction funnel (1) at its distal end and providing suction thereto; the suction funnel (1) has a first section (20) and a second section (30), the second section (30) being adjacent to the first section (20), the second section (30) having a gradually decreasing diameter, the suction funnel (1) being movably disposed within the delivery catheter (3) in a contracted state and at least partially outside the delivery catheter (3) in an expanded state, the suction funnel (1) including an impermeable covering, the diameter of the distal end of the suction funnel (1) being larger in the expanded state than in the contracted state; (C) a clot capture element (4) for capturing a thrombus; The clot capture element (4) is at least partially drawn into the suction funnel (1) together with the captured thrombus; (D) a microcatheter (5) for carrying the clot capture element (4) to the thrombus site; and The suction funnel (1) is formed of a mesh structure (13), and the mesh structure (13) is formed of a plurality of sets of spiral filaments that rotate in opposite directions and are intertwined with each other; the braid angle of the helical filaments of said first section (20) provides a greater outward radial force than said second section (30); The suction funnel (1) is configured such that its shape and length are adapted to contact the inner wall of the blood vessel, and the first section (20) of the suction funnel (1) contacts the inner wall of the blood vessel to reduce blood flow within the blood vessel; The suction funnel (1) extends in length as it narrows to retain the thrombus therein. The clot capture element (4) is movably disposed within the microcatheter (5) in a contracted state; The thrombectomy system is characterized in that the microcatheter (5) is movably disposed within the suction funnel (1).

2. The suction funnel (1), delivery catheter (3), clot capture element (4), and microcatheter (5) are movably arranged relative to one another so that their longitudinal directions are coaxial. The thrombectomy system of claim 1 .

3. The suction funnel (1) is self-expandable 3. The thrombectomy system according to claim 1, wherein the thrombectomy system comprises: a first thrombectomy unit;

4. The clot capture element (4) is a stent retriever device 4. The thrombectomy system according to claim 1, wherein the thrombectomy system comprises: a first thrombectomy tube;

5. The stent retriever device has a closed hole and a continuous framework.

5. The thrombectomy system of claim 4.

6. the first section (20) comprises at said distal end (11) a closed loop (23) acting as a spring; The radial force at both ends of the first section (20) is greater than that at its middle portion.

6. A thrombectomy system according to any one of claims 1 to 5.

7. The second compartment (30) has a first sub-compartment (31) and a second sub-compartment (32), The first sub-compartment (31) gradually decreases in diameter from the distal end to the proximal end to form a space for accommodating a thrombus; The second subcompartment (32) is tubular with a uniform diameter and provides a connection to the suction catheter (2).

7. The thrombectomy system according to claim 1.

8. The first sub-compartment (31) is frusto-conical 8. The thrombectomy system of claim 7.

9. The two sets of spiral filaments are aligned longitudinally as the suction funnel (1) narrows and lengthens.

9. The thrombectomy system according to claim 1.

10. The helical filament is formed of a metal, a metal alloy, or a composite material including nitinol or nitinol / platinum.

10. The thrombectomy system according to claim 1.

11. The percentage of platinum in the Nitinol / Platinum composite is in the range of 10%-40%.

11. The thrombectomy system of claim 10.

12. the number of spiral filaments is in the range of 24-48; the cross section of the helical filament is in the range of 40-60 μm; The angle of the helical filament relative to the longitudinal axis of the suction funnel (1) is: In the first section (20), it is in the range of 50-65°; In the second subsection (32), it is in the range of 15-50° 12. A thrombectomy system according to any one of claims 7 to 11.

13. the length of said first section (20) is in the range of 4-40 mm; the length of said second subsection (32) is in the range of 1-10 mm; The outer diameter of the first section (20) is in the range of 3.5-6 mm; the outer diameter of said second sub-section (32) is in the range of 1-2 mm; The shape of the first sub-compartment (31) has a generatrice inclined at an angle between 15 and 45° to the longitudinal axis of the suction funnel (1).

13. A thrombectomy system according to any one of claims 7 to 12.

14. The covering is made of a polymer including silicone or polyurethane.

14. The thrombectomy system according to any one of claims 1 to 13.

15. 2. The system for automatically inserting a thrombectomy system into a blood vessel according to claim 1, an automated proximal device (601) that provides a guide system for deploying said thrombectomy system (600); an imaging device (602) for displaying at least the location of the thrombus; A communication channel (603) for communication between devices constituting the system; a control module (604) for guiding the deployment of the thrombectomy system (600); a computer-aided controller (606) for controlling said control module (604); A data storage device (605) for storing data of the devices constituting the system; have A system for automatically inserting the thrombectomy system according to claim 1 into a blood vessel.

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