Vascular Reconstruction Device_NMPA Approval in March 2018
Product Name: Vascular Reconstruction Device
Category: Domestic Class III
Registration Pathway: Innovation
NMPA Approval Time: March 2018
Product Structure and Composition: The product consists of a stent system and a microcatheter system. The stent system comprises a stent (see Figure 1) and a delivery system, with the delivery system including a delivery wire and an introducer sheath; the microcatheter system consists of a microcatheter and a shaping needle. The stent is woven from nitinol alloy wire, and each stent is pierced by two platinum/iridium radiopaque wires throughout, released using a self-expanding method. The delivery wire is an interventional wire with radiopaque markers, made of nitinol alloy with a distal segment wound with a soft coil made of 304V stainless steel, and coated with a hydrophilic layer. The delivery wire, along with the stent, is preloaded into the introducer sheath, pushing the stent into the microcatheter through a delivery membrane on the delivery wire, and finally releasing it from the microcatheter. The microcatheter has a semi-rigid proximal shaft and a flexible distal end, with a non-X-ray opaque marker at the tip.
Scope of Application: This product is suitable for patients with unruptured aneurysms of the internal carotid and vertebral arteries, with an aneurysm neck ≥4mm and a maximum aneurysm diameter ≥10mm, and a target vessel diameter of 2.0mm-6.5mm.
Working Principle: Under the supervision of medical imaging equipment, the stent is delivered to the target lesion site within the microcatheter by advancing the delivery wire, released using a self-expanding method. The stent's mesh structure alters the hemodynamics of the aneurysm, reducing blood flow into the aneurysm sac, inducing thrombus formation inside the aneurysm, promoting intimal hyperplasia at the aneurysm neck, achieving the treatment goal of intracranial aneurysms.
Product Technical Requirement (PTR) Research: Stent: Material (chemical composition, microstructure); appearance; dimensions (stent outer diameter in the natural release state, stent wall thickness and stent horizontal segment length, nominal diameter vessel length covered by the stent, lower diameter vessel length covered by the stent, trumpet mouth diameter); radial support force; surface porosity; shortening rate; visibility; corrosion resistance; fatigue performance. Delivery wire: Appearance; dimensions (nominal length, maximum outer diameter); radiopacity; corrosion resistance; burst performance; bending performance. Introducer sheath: Appearance; dimensions (length, nominal outer diameter, inner diameter); fracture strength; compatibility performance. Stent system: Appearance; flexibility; pushability; stent release performance; delivery wire retraction performance; ethylene oxide residue. Microcatheter: Appearance; dimensions (proximal/distal outer diameter, inner diameter, effective length); breaking force; radiopacity; connectors (seats); leak-free; corrosion resistance. Shaping needle: Appearance; dimensions (effective length, outer diameter). Delivery system: Reducing substances; total heavy metal content; acidity and alkalinity; evaporation residue; ultraviolet absorbance. Stent and delivery system: Sterility; pyrogenicity. Microcatheter system: Reducing substances; total heavy metal content; acidity and alkalinity; evaporation residue; ultraviolet absorbance; ethylene oxide residue; sterility; pyrogenicity.
Other Performance Research: Product performance evaluation includes simulated use, MRI compatibility, stent finite element analysis, safety of nickel ion release, hemodynamics studies, etc., demonstrating that the product meets design input requirements.
Biocompatibility Research: The product consists of a stent system and a microcatheter system. The stent in the stent system is an implantable device that comes into long-term contact with circulating blood; the delivery system (including the delivery wire and introducer sheath) in the stent system is an externally accessed device that comes into short-term contact with circulating blood; the microcatheter system is an externally accessed device that comes into short-term contact with circulating blood. The applicant conducted biocompatibility evaluations of the implantable device and externally accessed devices according to the GB/T 16886 series of standards, including cytotoxicity; delayed hypersensitivity reactions; intracutaneous irritation; acute systemic toxicity; hemolysis; thrombosis; partial thromboplastin time; implantation test; genetic toxicity; subchronic toxicity.
Sterilization Research: The product undergoes ethylene oxide sterilization and is provided in a sterile state. The applicant provided a sterilization process validation report, demonstrating a sterility assurance level of 10-6. The ethylene oxide residue is not greater than 10µg/g, and the 2-chloroethanol residue level does not exceed 9mg per unit.
Product Service/Shelf Life and Packaging: The product has a shelf life of two years. The applicant provided a shelf life validation report, which included real-time aging verification, verifying product stability and packaging integrity.
Animal Experiment Research:
The purpose of the experiment was to evaluate the performance and safety effectiveness of the vascular reconstruction device in a New Zealand white rabbit animal model successfully creating an aneurysm. Two stents were implanted in each animal, and observations were made immediately post-implantation, at 4 weeks post-implantation, and at 3 months post-implantation, assessing the effectiveness of aneurysm treatment and the impact on perforator vessels.
Evaluation indicators include:
Device operability: Evaluating the ability of the delivery system to reach the target lesion, maneuverability, visibility, retraction ability, accuracy and effectiveness of stent release, stent visibility, suitability of dimensions, position, integrity and functionality, stent wall apposition in curved vessels, hemostasis of the delivery system and introducer sheath.
Device biocompatibility: Assessing intravascular thrombus formation, inflammatory response, endothelialization within the stent, and local bleeding and tissue necrosis near the stent implantation site.
Device effectiveness: Observing aneurysm occlusion rate and branch patency rate covered by the stent.
Animal experiment results indicate that the product meets the expected design requirements.
Clinical Evaluation:
The product underwent clinical evaluation through clinical trials. The clinical trial aimed to evaluate the safety and effectiveness of the product in treating unruptured intracranial aneurysms with a target vessel diameter of 2.0mm-6.5mm, an aneurysm neck ≥4mm, and a maximum aneurysm diameter ≥10mm in the internal carotid and vertebral arteries. The clinical trial was a prospective, multicenter, randomized controlled trial with the control group using vascular reconstruction devices combined with coil embolization.
The clinical trial was conducted at 12 clinical institutions, with 144 patients enrolled (82 in the trial group and 62 in the control group). The primary endpoint was the complete occlusion rate of the aneurysm at 6 months post-operation, with secondary effectiveness indicators including immediate procedural success rate, postoperative coil packing density within the aneurysm sac. Safety evaluation indicators included subjects' death or stroke related to the diseased vessel at 30 days post-operation, 90 days post-operation, and 1 year post-operation, target aneurysm bleeding, adverse event rate, stent stenosis, and stent thrombosis rate at 6 months post-operation. The Full Analysis Set (FAS) included 144 patients, with 82 in the trial group and 62 in the control group; the Per Protocol Set (PPS) included 126 patients, with 73 in the trial group and 53 in the control group; the Safety Set (SS) included 144 patients, with 82 in the trial group and 62 in the control group. The results of the primary/secondary effectiveness indicators are shown in Table 4. The results indicate a significant difference in the complete occlusion rate of the aneurysm at 6 months post-operation between the trial group and the control group, with a 95% confidence interval estimate supporting the hypothesis of the efficacy study.