Thrombectomy system and method for extracting a thrombus from a thrombus site in a patient's blood vessel

Abstract

Thrombectomy systems and methods for extracting thrombus are disclosed. The thrombectomy system includes a delivery catheter, an aspiration catheter including an aspiration funnel configured to be movably disposed within the delivery catheter in a retracted position and at least partially disposed outside the delivery catheter in an extended and expanded position, the funnel including an impermeable covering, the funnel configured to have its shape and length adapted to the surrounding blood vessel such that the funnel reduces blood flow through the blood vessel and lengthens as it narrows to retain thrombus within the funnel, a clot capture element configured to capture the thrombus and at least partially withdraw into the funnel with the captured thrombus, and a microcatheter adapted to carry the clot capture element to the thrombus. The clot capture element is movably disposed within the microcatheter in the retracted position. The microcatheter is movably disposed within the aspiration catheter.

Description

Technical Field

[0001] This invention generally relates to the field of medical devices. In particular, this invention relates to a thrombectomy system that allows for the removal of thrombi at the vascular level. The invention also relates to a method for extracting thrombi from a thrombus site in a patient's blood vessels. In some embodiments, the thrombectomy system includes a combination of an aspiration catheter and a clot-catching element. Background Technology

[0002] Acute ischemic stroke is a leading cause of morbidity and mortality, with an annual incidence of 118 cases per 100,000 people and a mortality rate of 29 cases per 100,000 people per year. These figures place ischemic stroke alongside cardiovascular disease and cancer as one of the leading causes of death in developed countries. To prevent or reduce complications associated with this disease and improve the prognosis of patients with ischemic stroke, it is essential to establish an appropriate reperfusion strategy as quickly as possible after clinical diagnosis. Until 2015, the preferred treatment for stroke was intravenous administration of recombinant tissue plasminogen activator (rtPA) 4.5 hours after symptom onset. However, this drug has a narrow therapeutic window and does not always reperfuse. Therefore, various devices ( Patients who have undergone intra-arterial recanalization therapy, such as mechanical thrombectomy, have had thrombus removal procedures performed. The aim is to remove the thrombus through aspiration, destruction, or capture / removal, which is considered a treatment option for patients unsuitable for rtPA or whose rtPA has failed. To improve the clinical outcomes of these devices, stent retrieval devices appear to have broadened the application of this technique (Solitaire™, etc.). and Revive).

[0003] Endovascular treatment for stroke has been available since the 1990s. The number of treated patients has increased slowly but steadily. A major obstacle to its wider adoption is the need for a coordinated healthcare system at different levels so that patients can reach a medical center capable of performing these highly complex treatments within 6-8 hours of symptom onset.

[0004] Early endovascular treatment strategies for stroke involve locally infusing a fibrinolytic agent into the thrombus via a catheter to dissolve the clot. Since the 2000s, devices have emerged that appear to be more effective than intra-arterial fibrinolysis. These are spiral structures that unfold around the thrombus to facilitate its extraction. (Retrieve system).

[0005] Starting in 2006, a new system became popular. Larger catheters were designed to be advanced to the thrombus. The catheter was connected to a continuous aspiration pump to aspirate the thrombus (Penumbra). ).

[0006] The system has been under development for years in an attempt to obtain catheters with increasingly larger diameters to be able to get close to blood clots.

[0007] In 2009, stent retrievers were introduced. Their use involves inserting a microcatheter through the thrombus. An internal prosthesis is then advanced through the microcatheter. Once the distal end of the microcatheter reaches the distal end of the thrombus, the internal prosthesis (stent retriever) is unsheathed, expands spontaneously through the thrombus, and captures it. It is recommended to wait a few minutes to allow the expanded internal prosthesis to properly engage the thrombus. The expanded stent is then withdrawn to drag the thrombus towards the catheter and away from the vessel. This final step can be done during aspiration through the catheter to attempt to reverse blood flow in the vessel and increase the likelihood of thrombus recovery. Additionally, a guiding balloon catheter is typically used when using stent retrievers. This catheter is advanced only to the extracranial carotid artery (away from thrombi located in intracranial arteries).

[0008] Due to their high efficiency and speed, stent retrievers have completely replaced the aforementioned first-generation devices. Several recent prospective randomized trials have demonstrated that stent retrievers-assisted mechanical thrombectomy and standard intravenous tissue plasminogen activator (IVtPA) thrombolysis have significant advantages over drug therapy alone (IVtPA) in revascularization of patients with acute ischemic stroke due to proximal large vessel occlusion.

[0009] However, the use of stent retrieval devices presents different unresolved challenges:

[0010] - Clot fragmentation. Stent retrieval devices can cause clot fragmentation, leading to distal embolism in new areas (previously unoccluded vessels). Current aspiration catheters have not overcome this limitation because the diameter of large-bore catheters is typically smaller than the clot size.

[0011] - Prolonged revascularization time because clot fragmentation requires multiple recanalizations.

[0012] - Navigability issues in small / tortuous blood vessels.

[0013] Most clots must be dragged unprotected from the occlusion site to the balloon-guided catheter, a long distance where the thrombus must be squeezed into it, again leading to potential loss of the clot or fragments detaching from it.

[0014] Once the clot is dislodged from the occlusion, blood flow resumes and moves in the opposite direction to the removal movement onto the unprotected clot. Therefore, any fragment or even the clot itself, if it detaches, can cause a new occlusion, known as a secondary embolism.

[0015] More importantly, current systems used to stop blood flow (primarily balloon catheters) must be placed upstream of the thrombus, rather than deep within the neurovascular system at the site of the thrombus. This means that circulation is restricted not only in the infarct area but also in broader brain regions, leading to the cessation of blood flow to brain regions unaffected by the clot itself.

[0016] Furthermore, despite advances in revascularization tools for large vessel occlusions presenting as acute ischemic stroke, a significant proportion of clots remain unsuitable for current strategies. Occlusions involving fibrin-rich thrombi are more difficult to recanalize than thrombi with a higher red blood cell content, often requiring more passes (Fennell VS et al., 2018). For example, calcified thrombi are harder and more difficult to remove using stent retrievers or aspiration methods compared to softer cardiogenic thrombi. Calcified lesions resist stent retraction. Calcified thrombi are also difficult to remove by aspiration because they have a harder consistency and tend to densely fill the vessel, making it difficult to place the catheter tip within the calcified clot to maintain the vacuum required for aspiration.

[0017] Several patent applications are known in this field. For example, US-A1-2018132876 discloses a system for removing thrombi from a blood vessel, including a stent retrieval device; a catheter configured to receive the stent retrieval device in a folded configuration, wherein the stent retrieval device is movable relative to the catheter; a sheath having a tubular body and defining a distal opening and a proximal opening; and a line connected to the stent retrieval device for positioning the stent retrieval device. The line extends through the proximal and distal openings of the sheath. The stent retrieval device is movable relative to the sheath, and the distal opening of the sheath is sized to allow the stent retrieval device to be withdrawn into the sheath without substantially compressing the stent retrieval device.

[0018] WO-A1-2015006782 discloses an apparatus and method for endovascular treatment of embolism. The apparatus includes a clot treatment device comprising a support member configured to extend through a delivery catheter and a plurality of clot-engaging members circumferentially positioned around a distal portion of the support member. The clot-engaging members are configured to penetrate clot material along an arcuate path and mechanically impregnate the clot, and release embolic particles upon re-insertion of the delivery catheter.

[0019] US-A1-2017119408 discloses a clot removal device comprising an expandable treatment member having a distal tip and a proximal end; a delivery line having a distal end coupled to the proximal end of the expandable treatment member; and a flow restrictor carried along the delivery line at a location separate from and close to the expandable treatment member. The flow restrictor has a body with a distal portion and a proximal portion, the distal portion being covered and the proximal portion being uncovered. The expandable treatment member is movable relative to the flow restrictor and can retract into the distal portion. Summary of the Invention

[0020] The problem this invention aims to solve is to improve the efficiency of currently used clot capture devices, particularly stent retrieval devices. This is especially useful for capturing hard clots (e.g., fibrin-rich clots).

[0021] According to a first aspect, the present invention provides a thrombectomy system. The proposed thrombectomy system includes: a delivery catheter configured to be advanced through a patient's vasculature to a thrombus site within a blood vessel; and an aspiration catheter adapted to apply aspiration to an expandable aspiration funnel extending from a distal end of the aspiration catheter, the aspiration funnel being configured to be movably disposed within the delivery catheter in a retracted position in a compressed state (delivery configuration) and at least partially disposed outside the delivery catheter in an extended and expanded position (also referred to herein as "expanded configuration"), the aspiration funnel comprising... A permeable covering, wherein the diameter of the distal end of the aspiration funnel is larger in the extended and expanded position than in the retracted position, the aspiration funnel being configured to adapt its shape and length to the inner wall of the blood vessel, such that the aspiration funnel reduces blood flow through the vessel and lengthens as it narrows to retain the thrombus within the aspiration funnel; a clot-catching element configured to capture the thrombus and at least partially retract it into the aspiration funnel along with the captured thrombus; and a microcatheter adapted to carry the clot-catching element to the thrombus site.

[0022] According to the invention, in particular, the clot-catching element is movably disposed within the microcatheter in its retracted position. Similarly, the microcatheter is movably disposed within the aspiration catheter. Furthermore, the different components of the thrombectomy system can move together or individually. In one embodiment, the interconnection between the components is achieved via a hemostatic valve.

[0023] Suitable thrombectomy devices for the purposes of this invention are described in patent application WO2016113047A1, the entire contents of which are incorporated herein by reference.

[0024] In a particular implementation, the delivery catheter, aspiration funnel, microcatheter, and clot-catching element are oriented on the same axis, coaxially configured, and independently movable.

[0025] In certain implementations, the suction funnel is self-expanding.

[0026] The thrombectomy system / device of the present invention can be used in neurovascular or peripheral vascular systems and is particularly suitable for navigation to the desired location and providing a clot seal at the most needed location, thereby preventing, for example, the development of secondary thrombosis. Its design allows for the introduction of a retrieval device that acts as a clot mobilizer, removing the thrombus by dragging it into the funnel opening. The method of the present invention involves guiding the thrombectomy device to a location close to the thrombus and retrieving the thrombus by a combination of aspiration and mechanical action. The aspiration funnel is a self-expanding covered stent that is operated using a catheter (e.g., a guide catheter) to enable navigation and positioning. Furthermore, the catheter is designed to maintain a vacuum near the thrombus from its proximal end to the distal end of the catheter, wherein the vacuum is generated by the interventional operator (e.g., with a syringe).

[0027] The covered aspiration funnel can be in a retracted or extended configuration, with the extended configuration having a larger diameter than the retracted configuration. Furthermore, the aspiration funnel is designed not to damage intracranial or peripheral arteries. Its design is intended to accommodate the diameter of the arteries, thereby restricting blood flow, which is one of the most important features of the system described for the prevention of distal embolism. Distal embolism is a typical clinical complication when the stent retriever passes through the clot or during retrieval.

[0028] In one implementation, the expansion behavior of the aspiration funnel is attributed to the nitinol material that forms it, thanks to its shape memory properties and superelasticity. Shape memory refers to the ability of a material to deform and then return to its original shape by heating it above its "transformation temperature." Combined with superelasticity, nitinol exhibits the correct properties to locate blood vessels of different diameters and geometries.

[0029] Furthermore, the advantages of the thrombectomy system can be summarized as follows: the aspiration funnel, which is a self-expanding stent (e.g., formed of nitinol) sealed with a polymer material membrane, expands and mimics the size of the blood vessel upon deployment. Advantageously, the large opening of the funnel, together with the clot-catching element, can aspirate the entire thrombus without breaking it, and also perfectly distributes the clot during removal. Clot loss is also prevented due to the long distance from the occlusion site to the outlet and also due to the large size of the clot (making it difficult to capture by the clot-catching element). The system can restrict blood flow in the vessel, thereby increasing the system's aspiration capacity and further reducing clinical complications, primarily distal embolism. Another key feature of the system is that, because blood flow is stopped not at the level of the carotid artery but directly at the thrombus site, only specific arterial branches are affected, rather than the entire hemisphere, thus improving the safety of the entire procedure. In summary, the thrombectomy system of the present invention offers significant advantages over other commercially available or soon-to-be-commercial devices.

[0030] The term "clot-catching element" in this specification should be understood as a device capable of interacting with a clot to capture and recover the clot from the bloodstream. This definition includes the following categories, but is not intended to limit the invention:

[0031] - Coil retriever system. This category includes first-generation clot-catching elements, such as... The retriever system is a spiral tapered cork screw similar to the tip of a catheter. The second generation introduced a spiral coil and an added filament at 90° relative to the proximal catheter. The third generation is a hybrid design of non-tapered, non-angled filament spiral coils to allow for maximum retention of clots.

[0032] - A stent retrieval device, as described in this specification, is a device typically equipped with a metal mesh, operated by a metal pusher, capable of capturing clots by retrieving them from within their supports. Examples of stent retrieval devices include the following:

[0033] οSolitaire FR (Medtronic Neurovascular)

[0034] οTrevo TM XP ProVue System Recovery (Stryker)

[0035] οEmbotrap(Neuravi)

[0036] οRetrieve PV(Revive PV)(DePuy Synthes)

[0037] οpReset(Phenox)

[0038] Eric (Microvention)

[0039] οMindFrame capture LP system (Covidien)

[0040] οAPERIO (Acandis GmbH)

[0041] οCatch(Balt Extrusion)

[0042] οTigertriever (Rapid Medical)

[0043] οStream (Perflow Medical)

[0044] οJrecan

[0045] ο3D revascularization device (Penumbra)

[0046] οNeva(Vesalio)

[0047] οVersi(Neurovasc Technologies)

[0048] Other types of clot-catching elements include:

[0049] Amnis Golden Retrieval System

[0050] οTriticum medicine

[0051] οClotTriever Thrombectomy Device (Inari Medical)

[0052] οDais-e(Mivi Neuroscience)

[0053] οNavimax (Intratech Medical)

[0054] οThromboWire(Capture Vascular Systems)

[0055] In a particular implementation, the clot-catching element is a stent retrieval device. More specifically, the stent retrieval device has a closed unit and a continuous skeleton, such as Solitaire. TM Blood regeneration device or Trevo Stentriever TM .

[0056] In one embodiment, the suction funnel includes sections defining a distal and a proximal end, and is formed by a mesh of at least two sets of identical or different helical filaments (or threads) rotating in opposite directions and intertwined with each other. The mesh includes a first tubular portion, particularly a first tubular portion having a uniform diameter, and a second tubular portion adjacent to the first portion and having a diameter smaller than that of the first tubular portion.

[0057] The first portion of the mesh has helical filaments with a braiding angle (β) adapted to provide a greater outward radial force, i.e., pressure, than in the second portion, so that the first portion better conforms to or overlaps with the inner wall of the blood vessel. The first portion may include a closed loop at the distal end configured to act as a spring, such that the radial force in the first and second ends of the first portion is higher than the radial force in the middle portion of the first portion.

[0058] The straight shape of the first part of the aspiration funnel creates a space that will contain the thrombus once it is aspirated. The first part conforms to the geometry of the blood vessel, and its outer surface overlaps with the inner wall of the vessel.

[0059] Specifically, the second part comprises two sub-parts, a first sub-part and a second sub-part. The first sub-part has a conical (or funnel-shaped) shape and includes a braided angle (α) that varies at its proximal and distal ends to provide radial strength to maintain the conical shape and reduce proximal blood flow during thrombus removal. The second sub-part comprises a tubular tube of uniform diameter configured to provide connection to an aspiration catheter.

[0060] Suction funnels of various sizes can be manufactured. In one embodiment, the first portion is longer than the second portion. In one embodiment, the length of the first portion is between 4 and 40 mm, and its outer diameter is between 3.5 and 6 mm, while the length of the second portion is between 1 and 10 mm, and its outer diameter is between 1 and 2 mm. Furthermore, the braiding angle (α) of the first portion relative to the longitudinal axis of the suction funnel is between 15 and 45 degrees. This angle is advantageous for having a greater radial force to impede flow, but at the same time, there is a seal for the blood vessel, which must also allow the suction funnel to be compressed.

[0061] In another embodiment, the non-permeable covering of the suction funnel comprises a polymer, such as silicone or polyurethane.

[0062] The helical filaments of the mesh can be made of metal, metal alloy, or composite material, including nitinol or nitinol / platinum, or Niti#1-DFTR. R (Draw-filled tubes) containing 10% to 40% platinum; particularly 20% platinum (Niti#1-DFTR). R -20% Pt). As the suction funnel becomes longer and narrower, the spiral filaments are adapted to become more longitudinally aligned.

[0063] In the embodiments, the spiral filament comprises a number ranging from 12 to 48 filaments, particularly 18 to 24 filaments. In this case, the cross-section of the filaments is in the range of 40 to 60 μm, particularly 50 μm, and the braiding angle (β) of the filaments relative to the longitudinal axis of the suction funnel is between 50 and 65 degrees for the first portion and between 15 and 50 degrees for the second sub-portion.

[0064] The aspiration funnel may also include or have one or more sensors attached thereto to provide information about it. For example, one or more illumination sensors may provide information about whether the aspiration funnel is in a retracted or extended position within the delivery catheter. Alternatively or additionally, the sensors may provide information about whether the aspiration funnel is well extended and extended, whether the thrombus is inside or outside, the composition of the thrombus, or the position of the funnel relative to the blood vessel. Alternatively, the sensors may include piezoelectric sensors that provide information about radial forces in each different section or subsection of the aspiration funnel. Alternatively, the sensors may provide information to differentiate between clot obstruction and intracranial atherosclerotic disease.

[0065] Advantageously, the aspiration funnel may also include at least one radiopaque marker at its distal end and / or other key points of the mesh, which allows the physician to know the precise location of the aspiration funnel when using fluoroscopy.

[0066] Another aspect of the present invention relates to a method for extracting a thrombus from a thrombus site in a patient's blood vessel, the method comprising:

[0067] The delivery catheter is advanced through the vascular system toward the site of the thrombus;

[0068] Place the distal end of the delivery catheter close to the blood clot in the blood vessel;

[0069] The aspiration catheter is advanced within the delivery catheter, and the aspiration funnel extends distally from the aspiration catheter.

[0070] Move the aspiration catheter and delivery catheter relative to each other to place the aspiration funnel outside the delivery catheter, which is close to the thrombus;

[0071] Expand the suction funnel to contact the inner wall of the blood vessel, thereby reducing the blood flow through the suction funnel;

[0072] The clot-capturing element is advanced distally toward the thrombus through a suction funnel;

[0073] Deploy the clot-catching element to capture the clot;

[0074] The clot-capturing element and thrombus are moved proximally toward the aspiration funnel;

[0075] Aspiration is applied to the aspiration funnel via the aspiration catheter to at least partially aspirate the thrombus into the aspiration funnel; and

[0076] The suction funnel and thrombus are moved proximally within the vascular system. The suction funnel adapts its shape and length to the surrounding vessels by lengthening as it narrows, thus retaining the thrombus within the suction funnel.

[0077] It should be noted that the steps of the proposed method can be performed in any order. In particular, the step of applying aspiration can be performed before or after the step of moving the aspiration funnel and thrombus proximally within the vascular system.

[0078] Optionally, the method may further include advancing a microcatheter within an aspiration catheter, with a clot-catching element disposed within the microcatheter. Furthermore, the method may also include moving the microcatheter and the clot-catching device relative to each other to position the clot-catching device outside the microcatheter; and extending the clot-catching device.

[0079] In the implementation, the expansion of the clot capture device includes allowing the clot capture device to expand itself.

[0080] In the implementation plan, advancing the microcatheter involves advancing the distal end of the microcatheter through the thrombus.

[0081] Optionally, the method may further include moving the clot-catching device at least partially proximal into the suction funnel.

[0082] In the implementation, the extended suction funnel includes allowing the suction funnel to expand on its own.

[0083] In one embodiment, the suction funnel includes a mesh of at least two sets of intertwined spiral filaments rotating in opposite directions, and the method further includes moving the two sets of spiral filaments to a more longitudinally aligned position as the suction funnel lengthens and narrows.

[0084] Another aspect of the present invention relates to a method for extracting a thrombus from a thrombus site in a patient's blood vessels, the method comprising:

[0085] The clot-catching element is advanced distally toward the thrombus site via the vascular system; and in particular, the clot-catching element self-extends toward the thrombus site;

[0086] The delivery catheter is advanced through the vascular system toward the site of the thrombus;

[0087] Place the distal end of the delivery catheter close to the blood clot in the blood vessel;

[0088] The aspiration catheter is advanced within the delivery catheter, and the aspiration funnel extends distally from the aspiration catheter.

[0089] Move the aspiration catheter and delivery catheter relative to each other to place the aspiration funnel outside the delivery catheter, which is close to the thrombus;

[0090] Expand the suction funnel to contact the inner wall of the blood vessel, thereby reducing the blood flow through the suction funnel;

[0091] The clot-capturing element and thrombus are moved proximally toward the aspiration funnel;

[0092] Aspiration is applied to the aspiration funnel through the aspiration catheter to at least partially aspirate the thrombus into the aspiration funnel; and

[0093] The suction funnel and thrombus are moved proximally within the vascular system. The suction funnel adapts its shape and length to the surrounding vessels by lengthening as it narrows, thus retaining the thrombus within the suction funnel.

[0094] By advancing the clot-catching element distally toward the thrombus site through the vascular system, the clot-catching element acts as an anchoring element, thereby achieving pushability / accessibility of the delivery catheter. Attached Figure Description

[0095] The foregoing and other advantages and features will be more fully understood from the following detailed description of the embodiments with reference to the accompanying drawings, which should be considered in an illustrative and non-limiting manner, wherein:

[0096] Figure 1 The illustration schematically shows the different portions of an aspiration funnel for extracting thrombi from blood vessels according to an embodiment of the present invention.

[0097] Figure 2 The diagram shows a grid included in different tubular sections of a suction funnel, with a lower grid density in the first section than in the second section.

[0098] Figure 3 The diagram illustrates some of the main specifications of the suction funnel.

[0099] Figure 4 This is a graph showing the ideal pressure versus diameter curve of the suction funnel.

[0100] Figure 5 This is a schematic diagram of the proposed thrombectomy system.

[0101] Figure 6-13 The steps of a method for removing a thrombus from a thrombus site in a patient's blood vessel using the thrombus removal system of the present invention are shown.

[0102] Figure 14 A model system of the cerebrovascular system is shown.

[0103] Figure 15 The revascularization rate after a single pass is shown in different models using soft red clots.

[0104] Figure 16 The revascularization rate after the third pass is shown in different models using soft red clots.

[0105] Figure 17The revascularization rate after a single pass is shown in different models using fibrin-rich clots.

[0106] Figure 18 The revascularization rate after the third pass is shown in different models using fibrin-rich clots.

[0107] Figure 19 The comparison of recanalization rates after the first and third passes is shown in in vitro studies (Example 1, sample size 50) and in vivo studies (Example 2), in the ANA+SR and BGC+SR groups. The absolute increase in recanalization rate of ANA+SR compared to BGC+SR was similar in both study models.

[0108] Figure 20 This is a diagram illustrating an automated thrombectomy system (ANCD) according to an embodiment of the present invention. Detailed Implementation

[0109] Figure 1 and Figure 2 A specific embodiment of the aspiration funnel 1 included in the proposed thrombectomy system / device (or ANCD) for retrieving thrombi from blood vessels is shown. The aspiration funnel 1 includes a segment 10 that is self-expanding and defines a distal end 11 and a proximal end 12, and can be shaped to fit the surrounding blood vessel, from a retracted position in a compressed state, for example, within a carrier (such as a delivery catheter 3), to an extended / expanded position once exiting the delivery catheter 3, in order to conform to the vessel wall to receive and retain the thrombus (THR).

[0110] like Figure 2 As shown, segment 10 includes a grid 13 having two sets of spiral filaments that rotate in opposite directions and are intertwined. In this embodiment, the grid 13 can follow a rhomboid or regular structure. The density of the grid 13 defines the elasticity of segment 10. As detailed in Table 1, the grid angle (or weave angle (β)) relative to the longitudinal direction can be variable.

[0111] The helical filament can be made of metal (including metal alloys), polymers, composites including nitinol or nitinol / platinum, or DFT. R (Draw-fill tube) and other materials with suitable mechanical properties.

[0112] from Figure 1 and Figure 2 As can be seen, grid 13 defines two distinct tubular sections, a first section 20 and a second section 30. In particular, the second section 30 comprises two sub-sections, namely a first sub-section 31 and a second sub-section 32.

[0113] like Figure 2As can be seen in this particular embodiment, the first portion 20 includes a closure loop 23 at its distal end 11, which facilitates the expansion of the segment 10 once it exits the aforementioned delivery catheter 3. Furthermore, these closure loops 23 act as springs or anchor points by restricting movement between the helical filaments and thus increasing the outward radial force. The closure loops 23 also provide a smooth distal end to reduce potential vascular injury and improve the patency of the aspiration funnel 1 within the vessel. The remainder of the first portion 20 creates a space that will accommodate the thrombus THR once it has been aspirated. The first portion 20 is adapted to the geometry of the vessel and, due to its configuration (e.g., diameter and braiding angle β), provides a higher outward radial force than in the second portion 30, allowing the segment 10 to better conform to the inner wall of the vessel. For example, the radial force in the distal end of the first portion 20 is particularly higher than in its intermediate portion due to the springing effect of the closure loops 23. Alternatively, the radial force in the first portion 20 can be evenly distributed along all its generatrices.

[0114] The first sub-section 31 (or the portion of the second section 30 adjacent to the first section 20) is conical or funnel-shaped. Due to its shape, this sub-section 31 has features that allow it to withstand blood pressure without collapsing. In the illustrated embodiment, the braiding angle (α) variation at the proximal and distal ends of the sub-section 31 provides radial strength to maintain the conical shape. The braiding angle (α) variation at the distal end of the sub-section 31 also works in conjunction with the closure loop 23 to hold the first section 20 in the open position and create space for the thrombus THR. The covering on the sub-section 31 impedes blood flow during the capture and removal of the thrombus THR and protects the captured thrombus THR during the withdrawal of segment 10 to the delivery catheter 3. This sub-section 31 is also a transition section from the larger diameter section 20 to the smaller diameter sub-section 32, which is used to connect to the aspiration catheter 2 (see...). Figure 5 Alternatively, it can be connected to a hypotube.

[0115] The second sub-section 32 (or the portion of the second section 30 adjacent to the proximal end 12) has a tubular, uniform diameter and provides a connection to the suction catheter 2. In some embodiments, the suction catheter 2 is a PTFE-lined braided catheter covered by an outer sheath. The braid and liner of the suction catheter extend distally from the outer sheath. A layer of polymer material may be placed around the protruding braid and liner, and a mandrel may be placed within the braid and liner. Subsequently, the second sub-section 32 of the segment 10 may be placed on this polymer portion, and another layer of polymer may be placed on the grid of the sub-section 32. The outer layer of the polymer material is then melted, allowing the polymer to flow through the small grids of the grid 13, removing the mandrel, thereby leaving a smooth surface across the entire suction catheter 2. This attachment method increases the structure and rigidity of the attachment portion of the suction catheter 2, and therefore the attachment portion should be as short as possible without compromising the integrity of the attachment between the segment 10 and the suction catheter 2.

[0116] As those skilled in the art will understand, other techniques can be used to connect segment 10 to the aspiration catheter 2. For example, in some other embodiments, if the aspiration catheter 2 is a metal thiocyanate tube, the mesh 13 of sub-section 32 is welded to a nitinol ring. This ring is welded directly to the thiocyanate tube. Alternatively, a stainless steel ring can be bonded to the mesh 13 of sub-section 32. The stainless steel ring is then welded to the thiocyanate tube. Another option is to engage segment 10 directly with a perforated ring, allowing the filament to pass through the perforation.

[0117] When segment 10 is compressed within the delivery catheter 3, segment 10 elongates to move the helical filament toward a longitudinally aligned state, thereby reducing the spring effect and facilitating the movement of segment 10 within the delivery catheter 3 by reducing friction and by increasing maneuverability. The maneuverability of segment 10 within the delivery catheter 3 is related to the patency of segment 10 within the artery.

[0118] The mesh angle or braiding angle (β) allows the mesh 13 to adapt to the curve of the blood vessel, avoids kinking, and creates free space within the mesh for unobstructed aspiration.

[0119] Now for reference Figure 3 Table 1 shows some of the main specifications of the suction funnel 1 according to the embodiment. Table 2 lists the measurement methods used to calculate these parameters.

[0120] Table 1. Main Specifications of Suction Funnels

[0121]

[0122]

[0123] Table 1 shows the parameters for a specific embodiment. In one embodiment, the parameters of the aspiration funnel 1 are as shown in Table 1 for large vessels (“Big Ref.”), for example, a diameter of 4.5 mm, such as the posterior portion of the carotid artery or the carotid siphon. In another embodiment, the parameters of the aspiration funnel 1 are as shown in Table 1 for small vessels (“Small Ref.”), for example, a diameter of 2.5 mm, such as the internal carotid artery (ICA) or the middle cerebral artery (MCA).

[0124] Table 2. Measurement methods for calculating different parameters.

[0125]

[0126] As described above, the aspiration funnel 1 can have two configurations: a retracted (or compressed) form within the delivery catheter 3 when near the thrombus site, and an extended and expanded (unfolded) form when not interacting with the delivery catheter 3 or the blood vessel. The parameters specified here relate to the natural (relaxed) form of the aspiration funnel 1, i.e., the extended and expanded (unfolded) position.

[0127] Segment 10 may include radiopaque markers made of platinum, tungsten, barium derivatives, gold, iridium, etc., located at its distal end 11 and / or within the grid 13, allowing the physician to know the precise location of the aspiration funnel 1 during fluorescence examination. Once fabricated, the radiopaque material can be deposited on a spiral filament (or dispersed on the surface of the coating if the aspiration funnel 1 has a coating). Alternative ways to make segment 10 radiopaque may be to use spiral filaments of different materials and opacity grades (e.g., nitinol and platinum). In certain embodiments, nitinol filaments with a platinum core are used. Similarly, the delivery catheter 3 may also include radiopaque markers.

[0128] Furthermore, segment 10 may have a coating, for example, covering only the first portion 20 or covering the entire segment 10. Figure 1 and Figure 2 In one embodiment, although not visible, the coating extends from the closed loop 23 to the sub-section 32. In one embodiment, the coating is applied at the junction of the segment 10 and the suction catheter 2 by immersing the segment 10 in a liquid polymer, thus curing the polymer. Optionally, the mandrel can be positioned within the grid 13 of the segment 10 while being immersed in the polymer coating material. Alternatively, the coating material can be sprayed onto the grid 13. In other alternative embodiments, the coating can be applied before the segment 10 is attached to the suction catheter 2. In such an embodiment, the coating does not reach the proximal end 12 of the sub-section 32, but there are uncoated spaces between the helical filaments, leaving them free to allow assembly with the suction catheter 2.

[0129] The coating prevents damage to the artery and avoids direct contact with the spiral filament. Furthermore, the coating provides a waterproof compartment, allowing the thrombus THR to be aspirated and protected during removal. In one embodiment, to apply the coating, the mesh 13 is attached to the delivery catheter 3, and then the coating is applied.

[0130] Internal or external glazes can also be applied to the coating to improve its performance. By applying a hydrophilic or hydrophobic coating to the outer surface of segment 10, the outer surface can be more easily transferred into the carrier and across the blood vessel by reducing the coefficient of friction. In the same way, by treating the inner surface of segment 10, the adhesion effect of the thrombus THR can be maintained once the thrombus appears inside.

[0131] The coating is made of an elastic material. In one particular embodiment, the coating of the suction funnel 1 is silicone resin. Alternatively, polyurethane or other types of plastic materials can be used. A mixture of polyurethane and silicone resin can also be used.

[0132] To achieve the dual properties of the coating (smooth outer surface of segment 10 and sticky or rough interior), the coating can be treated by adding the explained material, or these features can be incorporated into the structure of the mesh itself.

[0133] The coating may include holes to prevent the collapse of segment 10. Such holes can be formed after the coating is applied by drilling holes in the coating.

[0134] The dimensions of segment 10 depend on the size of the vessel in which it captures the thrombus THR. The dimensions of the sub-sections of segment 10 and the braiding angle of the mesh of auxiliary segment 10 provide reduced radial outward force when compressed into the delivery catheter 3 and provide sufficient outward force during expansion to avoid collapse due to blood pressure. Figure 4 A possible operating curve for one embodiment of section 10 is shown. The Y-axis defines the device pressure (mmHg), and the X-axis defines the arterial diameter (mm). The horizontal dashed line represents the blood pressure limit. In some embodiments, the arterial diameter range for which the suction funnel 1 of the present invention can be used is 2 to 5 mm. Section 10 is designed such that it can expand without being blocked by arteries with a standard operating range of 2 to 5 mm, and that it can handle blood pressures greater than 200 mmHg. Figure 4 As shown, this particular embodiment is not designed to be compressed to a diameter of less than 2 mm. The compression of segment 10 within the delivery conduit 3 results in a sufficiently high radial outward force to inhibit the advancement of the suction funnel 1 within the carrier.

[0135] Some embodiments of the present invention can be automated in both traditional (hospital) and non-traditional (nursing home, assisted care facility) environments, which can allow for greater deployment and use of ANCD and accelerate the removal of thrombus THR, thereby significantly improving patient outcomes because blood flow can be restored in a shorter time (e.g., to critical areas of the brain). One such automated device is described in WO2016 / 1113047.

[0136] When using an ANCD, segment 10 and its attached aspiration catheter 2 are advanced through delivery catheter 3 to the thrombus site within the patient's blood vessel. During advancement in delivery catheter 3, segment 10 is in a delivery configuration, where the first and second sets of helical filaments form a distally facing first angle relative to each other. As segment 10 emerges from delivery catheter 3, it begins to self-expand into an unfolding configuration. In an embodiment where mesh 13 forms a closed loop at the distal end of segment 10, the spring action of the closed loop of the helical filaments helps the first segment 20 expand to juxtapose with the blood vessel near the thrombus site. In the unfolding configuration, the first and second sets of helical filaments form a distally facing second angle smaller than the first angle (i.e., less longitudinal alignment of the filaments in the unfolding configuration compared to the delivery configuration). Sub-segment 31 also self-expands into a conical or funnel shape. The distal end of sub-segment 31 helps support the proximal end of segment 20 in the unfolding configuration.

[0137] The coating on the outer surfaces of sub-sections 31 and 20 reduces blood flow to the thrombus site. Optional perforations through the coating allow a small amount of blood to pass through the aspiration funnel 1 to prevent sub-section 31 from collapsing due to blood pressure and the pressure difference between the external blood pressure and the applied vacuum (internal). Once blood flow is reduced, aspiration can be applied through catheter 2 to the internal spaces of sub-sections 31 and 20 to aspirate the thrombus THR into section 20. The aspiration funnel 1 capturing the thrombus THR can then be removed from the patient. In the capture configuration (i.e., when the thrombus THR is internal), when the aspiration funnel 1 has a longer and smaller diameter shape, the first and second sets of filaments form a third angle facing the distal end, smaller than the first angle facing the distal end (i.e., the filaments become increasingly longitudinally aligned).

[0138] refer to Figure 5 The diagram shows a schematic of an extended configuration of the proposed ANCD, which in this particular embodiment includes an aspiration funnel 1, an aspiration conduit 2 connected to the aspiration funnel 1, a delivery conduit 3, a clot-trapping element 4, and a microcatheter 5. Detail A shows a schematic of an extendable tip aspiration conduit 7 including the aspiration funnel 1 and the aspiration conduit 2.

[0139] Figure 6-13The steps of a method for extracting a thrombus THR from a thrombus site in a patient's blood vessel using the ANCD of the present invention are shown. First, a delivery catheter 3 comprising an expandable tip aspiration catheter 7 is advanced over a guidewire 6 and a microcatheter 5 to the internal carotid artery ( Figure 6 Once the delivery catheter 3 reaches its position, it is withdrawn to open the opening of the expandable tip aspiration catheter 7. Figure 7-8 The aspiration funnel 1 expands to the diameter of the vessel and stops (i.e., obstructs or partially reduces) arterial blood flow. Figure 8 Once the opening of the aspiration funnel 1 is opened, the microcatheter 5 is advanced into the thrombus THR. Figure 9 Then the microcatheter 5 is withdrawn to deploy the clot-catching element 4, capturing the clot ( Figure 10 The clot-catching element 4 pulls the clot to the opening of the suction funnel 1, while simultaneously applying suction to the suction conduit 2 via a syringe to aspirate the clot. Figure 11 Finally, the clots adhered in suction funnel 1. Figure 12 ) and remove the system ( Figure 13 ).

[0140] The following details some specific experimental procedures. It should be noted that in the following experimental procedures, the combination of delivery catheter 3 and expandable tip aspiration catheter is referred to as the ANA device. Therefore, the proposed ANCD includes the ANA device, clot trapping element 4, and microcatheter 5.

[0141] Example 1: In vitro assay

[0142] 1. Research Objectives

[0143] This study aimed to evaluate the performance of the ANA device (i.e., the catheter device comprising a delivery catheter 3 and an expandable tip aspiration catheter 7) included in the ANCD. The expandable tip aspiration catheter 7 was constructed using a silicone-coated DFT (nickel-titanium / platinum) braided scaffold as defined below. Performance was evaluated in an in vitro 3D simulation model, a cerebrovascular model simulating intracranial circulation, including occlusive in vitro clot analogues, mimicking the physiological blood flow, pressure, and vascular anatomy of the carotid artery and brain.

[0144] Table 3

[0145]

[0146] Specifically, this study aims to evaluate the efficacy of combining the ANA device with a clot capture element 4 (e.g., a stent retrieval device (SR)) in terms of revascularization rate and clot embolism rate.

[0147] 2. Materials and Methods

[0148] 2.1 Sample

[0149] The ANA devices used in the study are as follows (Table 4):

[0150]

[0151] Commercially available devices are shown below (Table 5):

[0152]

[0153]

[0154] 2.2. Methods

[0155] The study was conducted at the animal facility of the de Recerca de Vail d'Hebrón (VHIR) in Barcelona, ​​Spain.

[0156] Mechanical thrombectomy was simulated in model cerebral vascular occlusion (including clot analogues) using the ANA device in combination with a stent retriever (Solitaire) and commercially available devices (Solitaire with a distal access catheter – “Solumbra-like” – and Solitair with a balloon-guided catheter). Furthermore, the performance of the ANA device, including patency and compatibility with different stent retrievers, was evaluated in the presence and absence of clots.

[0157] These procedures are followed by low-resolution fluorescence examination, assisted by trained technicians.

[0158] The model system of the cerebrovascular system includes a replica of human blood vessels and physiologically relevant simulated circulatory loops, as described below.

[0159] Blood vessel replicas

[0160] A three-dimensional in vitro model of intracranial circulation was used as a vascular replica.

[0161] Two models of blood vessel replicas were used:

[0162] 1. Vascular Models Jacobs InstituteThe model was designed based on vascular anatomy from 50 patients using CT-A imaging and then printed on a 3D printer (Jacobs Institute). The model closely resembles the human intracranial circulation in terms of curvature, diameter, and length, consisting of the internal carotid artery segment and branches of the middle cerebral artery (M1-M4 segments), bilateral A1 anterior cerebral artery segments connecting to a single anterior cerebral artery, and a single posterior communicating artery (right side), thus allowing for a near-complete circulation of the Willis cycle. Furthermore, it includes a representative pathway vascular system of the compressed aortic arc, common carotid artery, and internal carotid artery. The tortuosity levels of different portions of the vascular replica were moderate to severe, with mean tortuosity indices of 4.752 and 2.332 for the intracranial and pathway vascular systems, respectively, resulting in a complete model with a tortuosity index of 7.084.

[0163] 2. Vascular model UMASS (University of Massachusetts Medical School) Based on MRI angiography data from 20 patients, replicas of the Willis entire circulation with severe ICA siphonation in terms of curvature, diameter, and length were selected and fabricated using a low-batch manufacturing process. The selection of severely tortuous ICA siphons provided a challenging tortuous pathway for intravascular access. During image post-processing, the 3D reconstruction of the vascular system was modified to reincorporate the M2 and A2 partitions, resulting in individual outputs for each vascular region.

[0164] Two replicas of blood vessels with different curvatures were used:

[0165] (1) Moderate vascular model The mean tortuosities of different portions of the intracranial and access vascular system replicas were 5.831 and 0.047, respectively, resulting in a complete model with a tortuosity index of 5.878.

[0166] (2) Severe vascular model The mean tortuosity indices of different portions of the intracranial and access vascular system replicas were 7.067 and 7.067, respectively, resulting in a complete model with a tortuosity index of 7.233.

[0167] Simulated Circulating Loop

[0168] The model was connected to a peristaltic pump. A saline solution heated to 37°C was circulated through the model using the peristaltic pump. The flow rate into the intact neurovascular model was set to 370–450 mL / min, values ​​based on physiological flow rates. The pressure was also adjusted to 180 mmHg, the upper limit of clinically representative blood pressure. Flow and pressure sensors were located at the loop inlet, after the peristaltic pump output, while a second pressure sensor placed after the vascular replica calculated the differential pressure. A thermometer measured the fluid temperature in the intermediate zone. The intravascular device was operated under fluorescence examination guidance, and angiographic images of the vessel were obtained using contrast agent to determine the correct location of the target vessel.

[0169] 2.3. Agglomerates

[0170] To evaluate the efficacy (revascularization and embolization rate) in clot retrieval, soft, red, and fibrin-rich clots were used to induce occlusion of the middle cerebral artery (MCA, M1).

[0171] Porcine blood clots were prepared in VHIR. Soft, red, and fibrin-rich clots were prepared according to the methods of Mokin et al. (2016) and Duffy et al. (2017), respectively.

[0172] - Soft red clumps Mix 4 ml of non-anticoagulated swine blood with 32 mg of fibrinogen (F8630, Sigma-Aldrich) and 1 unit of thrombin-form bovine plasma (T4648, Sigma-Aldrich) for at least 3 minutes. Incubate the mixture at room temperature for at least 60 minutes.

[0173] - fibrin-rich clots After collecting pig blood, it was immediately anticoagulated using sodium citrate solution (3.2%). Whole blood components were then separated by centrifugation (600g, 15min, 4℃), and the extracted plasma was mixed with red blood cells (RBCs) at a ratio of 9:1. Coagulation was initiated by adding calcium chloride (2.06%), and the coagulated material was allowed to mature at 37℃ for 60 minutes. The resulting clot consisted of approximately 100% fibrin.

[0174] A clot (5x5x7mm) is injected into the flow circuit to form an MCA occlusion. Complete occlusion with TICI 0 is required before initiating thrombectomy.

[0175] 2.4. Procedure

[0176] The Neuron Max 088 guiding catheter (Penumbra) is placed in the cervical ICA and a guidewire is delivered, which is then gently advanced through the target vessel.

[0177] Thrombectomy (clot retrieval):

[0178] - Commercially available thrombectomy devices The microcatheter is routed through the guidewire that passes over the occluded clot. The guidewire is withdrawn, and then the stent retrieval device (Solitaire) is deployed for mechanical thrombectomy. During retrieval, continuous aspiration is performed with the aid of a 60 mL syringe.

[0179] - ANA combined with stent retrieval device Combining the ANA with a stent retrieval device to retrieve the clot: The funnel 1 with a stent is deployed to the proximal end of the occlusion. The microcatheter 5, containing the stent retrieval device (Solitaire), is passed along the filament through the aspiration catheter 2 and the deployed funnel 1 with the stent until it reaches and passes through the clot. The stent retrieval device is deployed to capture the clot while continuous aspiration is performed via the ANA. The stent retrieval device is dragged until the entire clot is safely placed within the funnel 1 with the stent. Finally, both devices are retrieved as a whole. Aspiration is not used in certain procedures.

[0180] 2.5. Evaluation Methods

[0181] (1) Effectiveness assessment:

[0182] Revascularization: Flow was assessed after all procedure time points following all procedure executions. TICI 2b and 3 were considered successful revascularizations (1). TICI 0, 1, and 2a were considered unsuccessful revascularizations (0). Time points:

[0183] • Baseline for the model vascular system before clot placement

[0184] • Pretreatment (ischemic baseline, clinical starting point)

[0185] • Following the first thrombectomy (“first revascularization”)

[0186] • After the second thrombectomy (if applicable)

[0187] • After the third thrombectomy (if applicable)

[0188] The primary endpoints considered in the effectiveness assessment are:

[0189] • Revascularization rate after the first pass (TICI 2b-3)

[0190] • Revascularization rate after 3 cycles (TICI 2b-3)

[0191] Embolic events (ENT / EDT). Flow is evaluated after the program time point following all program execution. Evaluation is performed for Distal Territory (EDT) and Emboli New Territory (ENT). An EDT score of 0 and an ENT score of 0 indicate no embolic event. An EDT score of 1 and an ENT score of 1 indicate an embolic event. Time point:

[0192] • Baseline for the model vascular system before clot placement

[0193] • Pretreatment (ischemic baseline, clinical starting point)

[0194] • Following the first thrombectomy (“first revascularization”)

[0195] • After the second thrombectomy (if applicable)

[0196] • After the third thrombectomy (if applicable)

[0197] The endpoint considered in the effectiveness assessment is:

[0198] • EDT and ENT after the first pass (TICI 2b-3)

[0199] • EDT and ENT after 3 sessions (TICI 2b-3)

[0200] (2) Roadworthiness assessment:

[0201] Accessibility was evaluated after the first attempt. The following endpoints were used to evaluate accessibility:

[0202] • Travel time [s]: The time required to reach the target blood vessel

[0203] • Accessibility / Flexibility: The ratio of passage time to score, indicating "device propulsion to the target vessel and proximal control of the device".

[0204] 2.6. Experimental Design

[0205] Table 6 shows the experiments conducted for each group and condition for different assessments. The maximum number of thrombectomy attempts was limited to 3.

[0206] Table 6. Experimental Design

[0207] The effectiveness of commercially available devices

[0208]

[0209]

[0210] The efficacy of ANA combined with a stent retrieval device

[0211]

[0212]

[0213]

[0214]

[0215] 2.8. Data Analysis

[0216] Revascularization and embolization values ​​are expressed as percentages; the mean for each group is calculated.

[0217] Qualitative analysis was performed on the performance scores. The mean and SD for each group were also calculated.

[0218] A qualitative assessment of the integrity of the data is conducted.

[0219] Statistical analysis of revascularization, embolization, and patency values ​​was performed using Excel. A t-test was applied to compare the means between the two groups; p < 0.05 was considered statistically significant.

[0220] 3. Results (expressed as a percentage)

[0221] Table 7 (intrac = intracerebral):

[0222]

[0223] For soft, red clots, the combination of ANA and Solitaire yields better or equal results than the combination of Solitaire with a balloon-guided catheter (BGC) or a distal access catheter (DAC). Figure 15 Similar results were observed in the first and third passes of all three models. Figure 16 ).

[0224] For fibrin-rich clots, the combination of ANA and Solitaire consistently yields better results than the combination of Solitaire with a balloon-guided catheter (BGC) or a distal access catheter (DAC). Figure 17 Similar results were observed in the first and third passes of all three models. Figure 18 ).

[0225] Similar results were observed using other stent retrieval devices (data not shown).

[0226] 4. Conclusion

[0227] Compared to other commonly used device combinations (such as BGC or DAC combined with a stent retrieval device), ANA combined with a stent retrieval device exhibits significantly better recanalization rates with fewer passes, especially for fibrin-rich clots.

[0228] Extrapolating these results to clinical practice, it appears that directly using ANA in combination with a stent retrieval device to treat large vessel occlusion and clinically mismatched acute ischemic stroke would be more effective. This combination would eliminate the need for rescue therapy.

[0229] Example 2: In vivo assay: Chronic evaluation of the performance and safety of ANA combined with clot-capturing elements (e.g., stent retrieval devices (SR)) in a porcine clot model.

[0230] 1. Introduction and Purpose

[0231] Endovascular therapy (EVT) is widely recognized as the most effective treatment for large vessel occlusion (LVO) stroke. Achieving the highest recanalization rate with the fewest attempts in the shortest time has been demonstrated to be associated with improved clinical outcomes. Despite its high efficacy, approximately 20% of treated patients have reportedly failed to achieve complete recanalization. To improve patient outcomes, various devices and combinations are being developed to increase the rate of complete recanalization on the first attempt. The development of such devices involves preclinical testing in phantom models that mimic the human anatomy of the cerebral blood vessels and in animal models that can assess device-associated vascular injury. Each phantom model has its own characteristics, therefore it is recommended that the efficacy and safety of any new device or combination be demonstrated under different conditions prior to the final evaluation in a first-in-human study.

[0232] The aim of this study was to evaluate the preclinical efficacy and safety of the combination of ANCD with an auxiliary device at 3 days and 30 days after three cycles in a porcine model, and specifically to confirm that the use of the self-expanding funnel 1 was not associated with higher vascular injury compared to the commonly used device.

[0233] The research design is as follows:

[0234] - Acute performance assessment on day 0 regarding the efficacy of vascular revascularization (clot repair).

[0235] - Angiography and histological evaluation at 3 days and 30 days to assess local and end-organ tissue response.

[0236] 2. Methods

[0237] In this case, the ANA device includes a delivery catheter 3 and an expandable tip aspiration catheter 7.

[0238] The expandable tip aspiration catheter 7 comprises a highly flexible polymer over a braided metal structure. It is designed to locally restrict blood flow during intervention. It includes a self-expanding funnel 1 that expands upon sheathing to the diameter of the vessel to accommodate its shape, thereby restricting blood flow. The expandable tip aspiration catheter 7 provides effective aspiration and serves as a supplementary mechanism when combined with a retrieval device. The aspiration funnel 1 is designed to be sufficiently flexible to accommodate the tortuosity of neurovascular structures. The aspiration funnel 1 comprises a radiopaque braid and a polymer membrane.

[0239] Delivery catheter 3 is the outermost catheter of the ANA device, which travels until it reaches the target blood vessel. It features a hydrophilic coating to reduce friction during use and a radiopaque marker at the distal end for angiographic visualization. The materials used allow for enhanced tip flexibility as well as sufficient rigidity and maneuverability in the proximal portion.

[0240] animal models

[0241] All animals were isolated and housed at CBSET (Lexington, MA, USA) for research purposes in a facility accredited by the American Society for Certification of Laboratory Animal Care and meeting or exceeding the requirements set forth in the USDA guidelines. Standard veterinary practices, including physical examinations and clinicopathology, were performed during isolation to determine the animals' health status prior to assignment to research. All animals were provided with a species-appropriate, nutritionally balanced diet daily and free access to water.

[0242] Eleven pigs (female or castrated male Yorkshire pigs, weighing 39-50 kg) were used in this study. Pigs were chosen as the experimental species because the size and anatomy of their vascular system are clinically relevant for testing catheter-based medical devices used to treat vascular diseases. Furthermore, pigs are widely accepted as the scientific standard for establishing animal models for vascular research.

[0243] Animals were anesthetized, cannulated, and IV catheters were inserted to administer supportive IV fluids and medications. The procedure was performed under aseptic conditions. Physiological parameters were monitored throughout the procedure. The femoral artery was accessed via an incision. A 9F guiding sheath was advanced into the artery, and heparin (150 U / kg, IV) was administered to prolong the activated clotting time (ACT) to approximately 200–350 seconds. ACT levels were monitored every 45 minutes throughout the procedure, and additional heparin was administered as needed to maintain the target ACT. An 8F Mach 1 IV catheter was inserted under fluorescence guidance. TMThe guiding catheter (CGC: Boston Scientific, Marlborough, MA) is advanced over the guidewire through a sheath into the descending aorta and target artery. Angiographic images of the vessels are obtained using contrast agent to determine the appropriate location of the treatment site. Angiography is performed throughout the procedure: at baseline, after each pass, and before autopsy. Parameters (qualitative and quantitative) for angiographic assessment include: vascular anatomy, target site, device monitoring, vascular status – injury, vasospasm, and blood flow (mTICI scale).

[0244] Two different recanalization strategies were tested according to the instructions for use (IFU) for intervention in the target vessel:

[0245] 1-BGC+SR: Balloon-guided catheter (BGC: 8Fr FlowGate2) TM Balloon-guided catheter (95cm); from Stryker Neurovascular, Fremont, CA) + stent retrieval device (SR: Solitaire) TM 2 4x40 mm; Medtronic Neurovascula), and

[0246] 2-ANA+SR.

[0247] The targets are the carotid and lingual arteries. These arteries cover a diameter range of 2.2 to 5 mm for ANA and SR, and a diameter range of 2.7 to 5 mm for BGC, representing the size of the target vessels in the cerebrovascular system (internal carotid artery (ICA) and middle cerebral artery (MCA)).

[0248] The ANA+SR and BGC+SR devices were distributed in the target vessels to ensure that all vascular beds were evaluated at each time point. Animal randomization was not required in this study because each animal underwent evaluation with both the ANA+SR and BGC+SR devices.

[0249] To study the device in a worse-case clinical simulation, three rounds of evaluation were performed in each study group under all conditions (the maximum number of deployments and retrievals allowed for the ANA device and Solitaire stent retriever, according to IFU). During the procedure, potential vascular injury (perforation, dissection, thrombosis) and vasospasm caused by the device were also assessed by angiography.

[0250] Clot preparation and delivery

[0251] Hard (high fibrinogen) and soft clots, previously generated from autologous blood (24–48 h), are applied to the target therapeutic vessels: the carotid and lingual arteries. Vessel and clot consistency are randomly selected to ensure uniform distribution of the test and control devices. Hard clots are prepared using whole blood samples (50 mL) collected in standard tubes, centrifuged, and the serum layer is extracted plus 10% of the underlying red blood cell layer, including the erythrocyte sedimentation rate (ESR) buffy layer. The extracted solutions are mixed and incubated for two hours. Porcine blood (up to 30 mL) is incubated at room temperature for two hours to produce soft clots. In both cases, the solid components are stored at 4°C in contrast-filled containers until the procedure is performed. Before application, the clot is cut to the appropriate size for the target vessel. The clot is introduced into the target area through an 8F guide catheter via a custom-made Luer connector to minimize shearing / fragmentation. Subsequent angiography is performed to confirm vessel occlusion (TICI 0). The clot is allowed to stabilize in the vessel 5–10 minutes before treatment, prior to thrombectomy.

[0252] Thrombectomy procedure

[0253] Mechanical thrombectomy procedures were performed using an ANA device in combination with a SR or a BGC to assess the ability to retrieve the clot. TICI flow (mTICI scale) and vasospasm were assessed after clot administration and each attempt at thrombectomy.

[0254] The intravascular device is operated under fluorescence examination guidance, and angiographic images of the blood vessel are obtained to determine the correct position of the device.

[0255] In all interventions, microcatheter 5 (Rebar 18, Medtronic Neurovascular) was advanced over a 0.014” microguidewire (Synchro; Stryker) to the proximal end of the occluded clot. In intervention 1, according to IFU and standard practice, the blood flow blockage was prevented by inflating the blood flow blockage globule (BGC) before thrombectomy using the SR; microcatheter 5 was positioned, and aspiration was performed through the BGC while the SR was being pulled out. In intervention 2, delivery catheter 3 was advanced close to the proximal end of the clot, and aspiration funnel 1 was deployed at the proximal end of the clot, creating a local flow blockage. Microcatheter 5 was then advanced through the clot, and the SR was deployed as usual. Microcatheter 5 was then completely withdrawn at this point to increase the suction force through the expandable tip aspiration catheter 7. The SR was then slowly pulled until its proximal end was within aspiration funnel 1, aspiration was initiated, and the ANA+SR was gradually pulled out together.

[0256] In all interventions, aspiration during the thrombectomy procedure was performed using a 60cc syringe (Vaclock; Merit Medical 1) connected to a three-way stopcock valve via a BGC (Intervention 1) or an expandable tip aspiration catheter 7 (Intervention 2). For each clot, recanalization attempts were repeated using the same strategy in two additional (final) attempts. Angiography was performed after each attempt to assess recanalization (TICI flow) and vasospasm. The recanalization rate (TICI 3) was calculated by considering the TICI data from the first and third attempts.

[0257] The research design results are summarized in Table 8 below:

[0258] Table 8. Study design: test apparatus (ANA, FlowGate BGC and Solitaire), number and location of blood vessels, number of animals involved and time point assessment.

[0259]

[0260] Histopathology

[0261] Animals were euthanized and subjected to full necropsy at 3 and 30 days post-treatment. Treated vessels were dissected, and relevant tissues / organs were collected, fixed in 10% NBF (neutral buffered formalin), paraffin-embedded, and stained with H&E (hematoxylin and eosin) and Verhoeff's for histological evaluation. Each treated vessel was trimmed to produce at least six cross-sections (2 proximal, 2 intermediate, and 2 distal) within the presumed treatment area. The proximal and intermediate portions were located within the deployment site of the test or control device, and the distal portions were located within the solitaire area. For tongue treatment, treated vessel sections were taken from bread slices of the tongue and may include surrounding thin-walled tissue. Additionally, distal portions of untreated vessels were obtained approximately 5 mm distal to the presumed treatment area.

[0262] Optical microscopy was used to determine histomorphological scoring parameters that reflect the extent and degree of the host's response to treatment of the target vessel / repair process. Histomorphometric markers included: vessel injury, vessel wall compression lesions, inflammation, endothelialization, intraluminal fibrin / thrombus deposition, neointimal formation, and adventitia fibrosis. Other microscopic changes in histological sections of the vessel were also examined, including the type and relative amount of hemorrhage, necrosis, and inflammatory cell infiltration. Any treatment-related adverse reactions, including thrombosis, necrosis, inflammation, and the presence of embolic material, were assessed in representative downstream tissue sections. Scores were calculated for each section and level, and the overall mean was reported for each vessel, with all markers ranked from 0 (no injury) to 3 (maximum possible degree of injury), with the exception of the endothelialization group, which was ranked from 0 (no endothelial coverage) to 4 (complete endothelial coverage). The pathologist was unaware of the treatment matrix during the pathologist's review.

[0263] Statistical analysis

[0264] Frequency statistics were obtained and compared using SPSS 17.0 statistical package (SPSS, Inc.). Statistical significance of differences between groups was assessed using Pearson's chi-square test or Fisher's exact test for categorical variables and Student's t-test and ANOVA for continuous variables. Mann-Whitney U- and Spearman tests were used when indicated. For all tests, a probability value < 0.05 was considered significant.

[0265] 3. Results

[0266] Angiography results

[0267] A total of 26 thrombectomy interventions were performed in 11 animals (BGC+SR: 13 interventions, ANA+SR: 13 interventions).

[0268] The results of the study using the ANA device and the FlowGate BGC (both in combination with the Solitaire device) are shown in Table 9, which shows the revascularization rates after the first and third passes for soft and hard clots.

[0269] Table 9. Repass rates for the first and third passes using ANA+SR and BGC+SR.

[0270]

[0271]

[0272] For soft clots, in both the first and third passes, combining ANA with Solitaire always yielded better results than combining Solitaire with a balloon-guided catheter (BGC).

[0273] For hard clots, in both the first and third passes, combining ANA with Solitaire always yields better results than combining Solitaire with a balloon-guided catheter (BGC).

[0274] After the first pass, the recanalization rates (TICI 3) were ANA+SR: 69% and BGC+SR: 46%. With additional passes, the recanalization rates increased in both treatment groups: ANA+SR: 100% vs BGC+SR: 77%. ANA+SR (1.4) tended to achieve complete recanalization with a lower mean number of passes compared to BGC+SR (1.9).

[0275] In terms of compatibility between device components and auxiliary devices, catheter maneuverability through anatomical structures, catheter radiopaqueness, and device integrity after use, the ANA device is similar to the FlowGate control. Compared to the FlowGate BGC, the ANA is slightly better in terms of vascular access / tracking and flexibility.

[0276] In the BGC+SR group, one distal embolism was observed by angiography and confirmed on day 3, while no distal thromboembolic event was observed in the ANA+SR group.

[0277] Angiography revealed three dissections during the intervention: one in the ANA+SR group and two in the BGC+SR group. None of these were related to the ANA or Solitaire device, as they were observed immediately after catheter insertion of the guide catheter or BGC into the target artery. The second dissection in the BGC+SR group was mild and no further complications occurred.

[0278] For occlusion, a total of 7 occurrences were observed at 3 or 30 days. Two occlusions were detected at 30 days (one ANA+SR and one BGC+SR), following severe dissection. Three occlusions (one ANA+SR at 3 days, and two BGC+SRs at 3 and 30 days) were considered inherent surgical complications. The last two occlusions (two BGC+SRs) observed during 3-day angiography were associated with failure to remove the clot after the procedure (up to three times). No vascular perforation was observed in either group. Vasospasm was a common finding to varying degrees in both groups. This is a common finding in porcine models, as porcines are prone to vasospasm.

[0279] Histological results

[0280] Histological evaluation was performed on a total of 24 vessels (2 out of 26 vessels were discarded due to severe dissection) and associated downstream tissues. On days 3 and 30, histological markers of vessel wall injury were absent or minimal in both the ANA+SR and BGC+SR groups and were comparable. Overall, all markers, including vessel injury, vessel wall compression inflammation, thrombosis, or hemorrhage, were absent or minimal, with scores below 1 or approximately 1 at both groups and time points. Endothelial coverage was lowest on day 3 (ANA+SR: 1.78 ± 1.22, BGC+SR: 2.03 ± 1.20; p = NS) and increased over time, reaching almost complete circumference by day 30 (ANA+SR: 3.77 ± 0.23, BGC+SR: 3.50 ± 1.07; p = NS).

[0281] Therefore, at days 3 and 30, vascular damage was absent or minimal in the ANA+SR and BGC+SR groups and was comparable, as no statistical difference was found. Other findings of inflammation, thrombosis, embolism, and necrosis in the downstream tissues of the carotid (brachialis) and lingual (tongue) arteries were also absent or minimal in both groups and at both time points, with most scores being 0 and below 1.

[0282] 4. Conclusion

[0283] This study in the porcine clot model shows that, compared with Solitaire TM The combined ANA device offers comparable safety to balloon-guided catheters with the same stent retrieval device. Furthermore, despite differences in vascular tortuosity and experimental conditions, the observed efficacy curves were similar to those obtained in previous preclinical studies using 3D-printed phantoms (Example 1).

[0284] Histopathological analysis confirmed that the ANA device did not have a harmful effect on the arterial wall, exhibiting minimal findings comparable to the BGC+SR group. To characterize safety in a simulated real-human case, target arteries were selected with diameters of 2.2–5 mm. These diameters are smaller than those typically found in arterial segments where guide catheters and BGCs are placed. This may explain the few arterial dissections and occlusions observed prior to ANA / SR deployment that occurred after guide catheter / BGC manipulation.

[0285] The innovative design of the aspiration funnel 1 (a self-expanding braided assembly that adapts to the vessel wall) combined with aspiration and subsequent local vacuum intuitively suggests a significantly greater vascular risk than conventional endovascular devices used in routine neurothrombosis resection. However, based on these results, the design of the aspiration funnel 1 and the entire ANA device is non-invasive to the vascular system, primarily due to the balanced radial force of the aspiration funnel 1, which is sufficient to adapt to the vessel and allow aspiration without excessively damaging the vessel wall, and the smooth silicone coating of the aspiration funnel 1. Furthermore, the catheter surface and tip are smooth with a lubricating coating, facilitating access and avoiding vascular trauma. Histopathological and angiographic evaluations demonstrate the good safety profile of the resection vessel. These evaluations clearly show that vascular injury caused by the ANA device combined with SR is unrelated to and dissimilar to BGC+SR, as histomorphological marker scores are absent or extremely low, no perforation occurred, and dissection was unrelated to the ANA device but related to the procedure (BGC or guiding catheter).

[0286] Notably, the ANA device combined with the stent retrieval device achieved a high complete recanalization rate with a lower number of passes; therefore, the proposed ANCD has better efficacy than current commercial 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 showed similar recanalization results in both models and real patients may indicate that the results from human clinical studies utilizing ANCD will be consistent with those currently obtained in preclinical models.

[0287] Recent publications indicate that not only is a higher degree of recanalization associated with better outcomes, but achieving the same degree of recanalization with fewer passes (ideally in a single pass) is also a predictor of improved long-term outcomes. These publications also note that currently approved and widely used thrombectomy devices and combinations achieve 40-50% first-pass complete recanalization rates. Newer devices, such as the proposed ANCD, with improved efficacy properties, can increase the success rate of both the first and final passes and may improve short- and long-term outcomes for stroke patients undergoing EVT.

[0288] The ANA device, and the corresponding ANCD, are designed to induce local blood flow occlusion while completely aspirating the clot into the aspiration funnel 1 to prevent fragmentation and distal embolism. These features are supported by preclinical observations in an in vitro model printed from a phantom (Example 1) and in this animal study using both soft and hard clots. These encouraging results cannot be used as a predictor of the success rate of a similar first attempt in human studies, but may represent the best preclinical evidence available at this stage. Furthermore, the results observed in this study indicate that the safety profile of ANA+SR is similar to that of the commonly used BGC+SR combination.

[0289] The research reported was conducted in an independent facility in accordance with good laboratory practices, and the results were obtained directly from official regulatory reports.

[0290] The conclusion can be summarized as follows:

[0291] 1. Preclinical results from the porcine clot model support the high efficiency of ANA+SR without causing clinically significant vascular damage that may be associated with the novel funnel assembly.

[0292] 2. The efficacy curve in this in vivo study is similar to that in the in vitro phantom model (Example 1, Figure 19 When used in conjunction with a stent retrieval device, the ANA device enhances its effectiveness in mechanical thrombectomy while maintaining a similar safety profile to commonly used devices.

[0293] 3. This study demonstrates that the ANCD outperforms the FlowGate™ balloon guide catheter in terms of handling, positioning, propulsion, and tracking.

[0294] 4. There were no treatment-related health or clinical problems, and all animals survived to the predetermined endpoint. The pathologist reported that on days 3 and 30, with Solitaire... TM ANA used in conjunction with 2 revascularization devices has the same characteristics as Solitaire. TM 2. Control group using FlowGate in conjunction with revascularization device TM Balloon-guided catheter devices allow for comparison of tissue responses.

[0295] Example 3: Human Clinical Trial: A prospective, single-arm, multicenter study to evaluate the safety and performance of an ANA device combined with a clot capture element (e.g., a stent retriever (SR)) in patients with acute ischemic stroke.

[0296] The first patient in the following clinical trial was enrolled on September 21 last year and is currently in progress.

[0297] 1. Introduction and Purpose

[0298] As previously described, the ANA device is a distal access catheter designed to assist neurovascular surgery by facilitating the insertion and guidance of other devices (i.e., retrieval devices and endovascular catheters) and restricting blood flow to a target location. In this particular embodiment, the ANA device is a sterile, single-use, disposable endovascular device comprising two coaxial catheters (delivery catheter 3 and expandable tip aspiration catheter 7), the coaxial catheters being composed of segments of varying stiffness. The expandable tip aspiration catheter 7 comprises a radiopaque nitinol braid (self-expanding funnel 1) covered with a continuous silicone coating, providing local and temporary blood flow restriction when the expandable tip aspiration catheter is deployed. The delivery catheter 3 has a hydrophilic coating to reduce friction during use and is marked with radiopaque markings at its distal end. Both catheters 1 and 7 have Luer locking hubs at their proximal ends.

[0299] This proposed study aimed to collect prospective clinical evidence to compare the ANA device with similar devices used to guide and support stent retrievers during neurothrombosis resection. The protocol was designed to replicate the patient population previously involved in studies with similar devices. The primary endpoint was the ability of the ANA device to facilitate stent retriever deployment and neurothrombosis resection in the anterior circulation. Successful reperfusion was defined as achieving a modified intracerebral infarction thrombolysis (mTICI) score ≥2b in the target vessel within ≤3 passes using the ANA device without the use of rescue therapy. Follow-up was conducted at 24 hours, day 5 (+ / - 12 hours) or discharge (whichever comes first), and day 90, allowing for recording of clinical outcomes and other complications throughout the neurothrombosis resection procedure, with remote access utilizing the ANA device. This study was conducted in accordance with ISO 14155 (Clinical studies of medical devices for human subjects – Good clinical practice).

[0300] The aim of this study was to evaluate the safety and performance of the ANA catheter system as a tool, facilitate the placement of the Solitaire stent retrieval device, and provide temporary flow restriction for stroke patients undergoing neurothrombosis resection for acute large vessel occlusion (LVO) within 8 hours of symptom onset (to the neuroimaging laboratory) (for the last good observation of the subject).

[0301] 2. Methods

[0302] Primary endpoint:

[0303] Performance has been evaluated for the ability of the ANA device to facilitate stent retrieval device deployment and neurothrombosis resection in the anterior circulation. Successful reperfusion was defined as achieving a modified thrombolysis for stroke (mTICI) score ≥2b in the target vessel within ≤3 passes of the ANA device without the use of rescue therapy.

[0304] Safety was assessed for all serious adverse device effects occurring within up to 90 days post-surgery, including symptomatic intracranial hemorrhage (sICH) within 24 hours (-8 / +12 hours) post-surgery.

[0305] Secondary endpoint:

[0306] The secondary performance endpoints of this study are as follows:

[0307] -The ability of the ANA device to reach the occlusion in a large, passable blood vessel and deploy a stent retrieval device to attempt neurothrombosis removal and at least through the internal carotid bulb in the anterior cerebral circulation.

[0308] - Operation time is defined as the time from perforation to achieving mTICI ≥ 2b in ≤ 3 passes or (if not obtained) reaching final angiography.

[0309] - Treatment time is defined as the time from entry to puncture to the first baseline angiography and the time to achieve mTICI ≥2b in ≤3 passes or (if not achieved) to the final angiography.

[0310] - Neurological status at day 5 (+ / - 12 hours) or at discharge (whichever comes first) and at day 90 (+ / - 14 days), determined by NIHSS score.

[0311] - Modified Rankin Scale (mRS) score on day 5 (+ / - 12 hours) or at discharge (whichever comes first) and 90 days.

[0312] The secondary safety endpoints of this study are as follows:

[0313] - Assessment of intracerebral hemorrhage (ICH); any symptomatic or asymptomatic ICH assessed by magnetic resonance imaging (MRI) / computed tomography (CT) within 24 hours (-8 / +12 hours). ICH is defined as any extravascular blood flow within the brain or skull. ICH is considered symptomatic if it is associated with clinical deterioration (deteriorating NIHSS score >4) or death, and is identified as a primary cause of neurological deterioration (as determined by an independent clinical events committee).

[0314] - The incidence of neurological function deterioration >4 points on the NIHSS within 24 hours (-8 / +12 hours), as assessed by an independent investigator (i.e., not involved in patient screening or thrombectomy procedures).

[0315] - Embolism occurred in an area not previously explored on cerebral angiography.

[0316] -Surgery-related mortality rate on day 5 (+ / - 12 hours) or at discharge (whichever comes first).

[0317] - Surgical complications: arterial perforation, arterial dissection and vasospasm in the target vessel, as well as embolism in previously unexplored vascular areas.

[0318] - Infarction occurs in previously unexplored vascular areas, as assessed by imaging (MRI / CT) 24 hours postoperatively.

[0319] Study locations and population sample size :

[0320] The study has been conducted at up to five (5) large-capacity, comprehensive stroke centers (available 24 / 7) within the EU. Currently, the proposed location is in Spain, but other European countries may be added later. The stroke centers involved are Germans Trias i Pujol Hospital, de Bellvitge Hospital, Clínic Hospital, Vail d'Hebron Hospital, and lasCruces de Bilbao Hospital.

[0321] This population is based on patients with acute ischemic stroke (AIS) attributable to occlusion of large arteries in the neurovascular system (e.g., the internal carotid artery, the M1 or M2 segment of the middle cerebral artery), and those who do not meet the criteria for IV alteplase (tissue plasminogen activator [t-PA]) or who received IV t-PA therapy but did not achieve adequate recanalization, but were in the catheter insertion laboratory within 8 hours from symptom onset (last good result) to groin perforation. One hundred and twenty-five (125) consecutive subjects were enrolled for treatment with the ANA device in combination with the Solitaire stent retriever. The inclusion and exclusion criteria for patient selection are detailed in the clinical trial protocol.

[0322] It is estimated that the study will require approximately 5 to 6 patients per month per center, or 25 to 30 patients per month, for a duration of 5 to 6 months, to recruit 125 participants. Each patient will participate for a duration of 90 days + / - 2 weeks. As part of the analysis, interim analyses will be conducted and interim study reports prepared when patients are at day 35 (+ / - 12 hours) or discharged, including primary performance and early secondary endpoints.

[0323] For statistical analysis purposes, the following study population was defined:

[0324] - The recruited group: defined as all participants who have given informed consent to participate in the study.

[0325] -Intent-To-Treat (ITT): Defines all subjects recruited in this study who are intended to undergo surgery.

[0326] - Modified Intention-to-Treat (mITT): Defined as all subjects in the ITT analysis set excluding transfer subjects. Transfer subjects are defined by each investigator's first subject.

[0327] Research procedures and evaluation:

[0328] Table 10 below shows the protocol for assessments recorded at baseline, during the procedure, and at follow-up office visits that should be completed at 24 hours post-operation, day 5 (+ / - 12 hours) or discharge (whichever comes first, depending on the earliest time point), and 90 days post-operation.

[0329] Table 10: Evaluation Scheme

[0330]

[0331]

[0332] For any patients not included in the study, all thrombectomy patients who visited the study site after the start of the study were anonymized and followed up in the patient screening log; the reasons for non-enrollment were recorded in the screening log.

[0333] Analysis method:

[0334] Using SAS For version 9.4 or later, perform statistical analysis and prepare a complete statistical analysis plan before conducting the analysis: provide a complete description of all derived variables used in the report, as well as the statistical tables and lists to be generated.

[0335] All statistical analyses were performed on the locked database after the data management process resolved the data clarification.

[0336] The primary analysis set for the statistical report was the ITT population, and no missing data were replaced in the statistical analysis to provide unbiased results. However, two sensitivity analyses were performed on missing values ​​for the primary performance endpoint. The first estimated failures rather than missing values ​​using a conservative approach. The second estimated missing values ​​with the same repartitioning using a repartitioning of successes / failures reported for non-missing values. The same statistical tests were provided in both sensitivity analyses. Furthermore, the primary endpoint was reported for the mITT population.

[0337] Apart from the primary performance endpoint, no statistical tests were performed on any parameters in the study; only descriptive analyses were provided to fully describe the recorded parameters. The primary performance endpoint was analyzed using a binomial test, as described in the study protocol (Section 15.1). Heterogeneity of the primary endpoint outcomes was assessed by comparing the percentage of success between locations using a two-sided chi-square test at the 5% level. Furthermore, the same analyses were provided by pooling locations from the same town. These analyses were performed only for the ITT population.

[0338] Interim analyses and interim study reports were conducted when participants were on day 5 (+ / - 12 hours) or discharged, including primary performance and early secondary endpoints.

[0339] Continuous variables are summarized using standard quantitative statistics: number of non-missing observations, mean, standard deviation, median, quartiles, and range (minimum and maximum observations). The number of missing observations is also specified.

[0340] Categorical variables are summarized using classic frequency statistics: the number of non-missing observations and the percentage of each class. The percentage is calculated based on the number of non-missing observations. The number of missing observations is also specified.

[0341] Where applicable, the bilateral asymptotic or exact confidence interval (CI) of the binomial distribution is calculated at the 95% level (unadjusted 95% CI).

[0342] The primary endpoint and early secondary endpoints were assessed in the ITT and mITT populations. Other secondary endpoints were assessed only in the ITT population.

[0343] AE data were summarized using descriptive statistics: the total number of events and the number of subjects with at least one of the corresponding categories of AE, ADE, SAE, SADE, and device defect. Severity and causal relationships were presented.

[0344] Now for reference Figure 20This figure depicts another embodiment of the proposed thrombectomy system (or ANCD) 600, which allows for automated operation via a vascular system. According to this particular embodiment, an automated proximal device 601 provides a guidance system for deploying the ANCD 600. Furthermore, an imaging device 602 can detect radiopaque markers included in segment 10 and also in the delivery catheter 3, and a communication channel 603 can be used to provide means for transmitting images to a control module 604. The control module 604 is programmed or configured to allow guidance for the deployment of the ANCD 600 and data storage on a data storage device 605. The control module 604 can be a programmable logic controller, a computer, etc. In this particular embodiment, the control module 604 is guided by a computer-aided controller 606. The communication channel 603 can be an Ethernet grid, WiFi, Bluetooth, etc. The control module 604 is programmed to instruct physicians or technicians to operate the ANCD 600, which allows the ANCD 600 to be used in non-hospital environments, such as nursing homes or assisted living facilities.

[0345] By allowing the ANCD 600 to be used "on-site," the time required for thrombectomy is greatly reduced, thus significantly improving patient outcomes. It can also be controlled via a controller, such as those used in other current medical devices. In another embodiment, the system can be manually controlled.

[0346] Although the invention has been described and illustrated above with reference to certain specific embodiments, it is not intended to be limited to the details shown. Rather, various modifications to the details may be made within the scope and extent of equivalents of the claims.

[0347] The scope of this invention is defined by the appended claims.

[0348] References cited

[0349] Fennell VS, et al. "What to do about fibrin rich'tough clots'? Comparing the Solitaire stent retriever with a novel geometric clot extractor in an invitro stroke model", J NeuroIntervent Surg 2018; 0:1–4. doi:10.1136 / neurintsurg-2017-013507.

[0350] Duffy S,Farrell M,McArdle K,Thornton J,Vale D,Rainsford E,Morris L,Liebeskind DS,MacCarthy E,Gilvarry M.Novel methodology to replicate clotanalogs with diverse composition in acute ischemic stroke.J NeurointervSurg.2017May;9(5):486-491.

[0351] Mokin M,Setlur Nagesh SV,Ionita CN,Mocco J,Siddiqui AH.Stentretriever thrombectomy with the Cover accessory device versus proximalprotection with a balloon guide catheter:in vitro stroke model comparison.JNeurointerv Surg.2016 Apr;8(4):413-7.

Claims

1. A thrombectomy system, comprising: A delivery catheter configured to be advanced through the patient's vascular system to the site of a thrombus within a blood vessel; A suction catheter adapted to apply suction to an expandable suction funnel extending from a distal end of the suction catheter, the suction funnel including a first portion and a second portion adjacent to the first portion, the second portion providing a reduced diameter, the suction funnel being configured to be movably disposed within the delivery catheter in a retracted position in a compressed state, and at least partially disposed outside the delivery catheter in extended and expanded positions, the suction funnel including an impermeable covering, the diameter of the distal end of the suction funnel being larger in the extended and expanded positions than in the retracted position; A clot-catching element configured to capture a thrombus and, together with the captured thrombus, at least partially retract it into the aspiration funnel; as well as A microcatheter adapted to carry the clot-capturing element to the thrombus site. in: The suction funnel is formed by at least two sets of meshes of spiral filaments that rotate in opposite directions and are intertwined with each other. The mesh of the first portion has spiral filaments with braided angles, which are configured to provide a greater outward radial force than that of the second portion. The suction funnel is configured to fit its shape and length to the inner wall of the blood vessel, such that a first part of the suction funnel is against the inner wall of the blood vessel to reduce blood flow through the blood vessel, and that the suction funnel becomes longer as it narrows to retain the thrombus within the suction funnel. The clot-catching element is configured to be movably disposed within the microcatheter in a retracted position, and The microcatheter is configured to be movably disposed within the aspiration catheter.

2. The thrombectomy system of claim 1, wherein the delivery catheter, the aspiration funnel, the microcatheter, and the clot-catching element are oriented on the same axis, coaxially configured, and movable relative to each other.

3. The thrombectomy system according to claim 1, wherein the aspiration funnel is self-expanding.

4. The thrombectomy system of claim 1, wherein the clot capture element is a stent retrieval device.

5. The thrombectomy system of claim 4, wherein the stent retrieval device has a closed unit and a continuous skeleton.

6. The thrombectomy system according to claim 1, wherein: The first portion includes a closed loop at the distal end, which is configured to act as a spring such that the radial force at the first and second ends of the first portion is higher than the radial force in the intermediate portion.

7. The thrombectomy system of claim 6, wherein the second portion comprises two sub-parts, the first sub-part having a gradually decreasing diameter shape and configured to open and form a space for the thrombus, and the second sub-part having a tubular uniform diameter and configured to provide connection to the aspiration catheter.

8. The thrombectomy system of claim 7, wherein the shape of the first sub-part is conical.

9. The thrombectomy system of claim 1, wherein as the aspiration funnel becomes longer and narrower, the two sets of spiral filaments are adapted to become more longitudinally aligned.

10. The thrombectomy system of claim 1, wherein the helical filaments of the mesh are made of metal or a composite material including nitinol.

11. The thrombectomy system of claim 10, wherein the helical filaments of the mesh are made of a composite material comprising nitinol and platinum, wherein the percentage of platinum is 10% to 40%.

12. The thrombectomy system according to any one of claims 7 to 8, wherein: The number of the spiral filaments is between 24 and 48, and the cross-section of the filaments is between 40 and 60 μm; and The angle of the spiral filament relative to the longitudinal axis of the suction funnel is between 50 and 65 degrees for the first portion and between 15 and 50 degrees for the second sub-portion.

13. The thrombectomy system according to any one of claims 7 to 8, wherein: The length of the first portion is in the range of 4 to 40 millimeters, and the length of the second sub-part is in the range of 1 to 10 millimeters; The outer diameter of the first portion is in the range of 3.5 to 6 mm, and the outer diameter of the second sub-part is in the range of 1 to 2 mm; and The shape of the first sub-part includes a generatrix, the angle of which relative to the longitudinal axis of the suction funnel is between 15 and 45 degrees.

14. The thrombectomy system of claim 1, wherein the covering comprises a polymer, the polymer comprising silicone or polyurethane.

15. A system for automatically operating the thrombectomy system of claim 1 onto a blood vessel, the system comprising: Automated proximal device configured to provide a guidance system for deploying a thrombectomy system; imaging device; communication channel; Control module, configured to allow the deployment of the thrombectomy system; data storage device; And a computer-aided controller, configured as a guide control module.

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