Neurothrombectomy Devices for Acute Ischemic Stroke Treatment - Pre-clinical and Clinical Testing
This guidance outlines FDA's recommendations for pre-clinical and clinical studies for neurothrombectomy devices intended to retrieve or destroy blood clots in cerebral neurovasculature for ischemic stroke treatment. It covers mechanical (snare or suction), laser, ultrasound technologies, or combination of technologies.
What You Need to Know? 👇
What regulatory pathway should I follow for my neurothrombectomy device?
The pathway depends on your device technology and predicate identification. Mechanical devices are typically Class II (510(k)), while novel technologies may require de novo classification or PMA if no substantial equivalence can be established.
What are the key inclusion criteria for neurothrombectomy clinical studies?
Include patients with angiographic evidence of treatable occlusion (TIMI grade 0-I flow), NIHSS ≥4, and treatment initiation within 8 hours of symptom onset. Stratify randomization by NIHSS scores for balanced comparison.
What safety endpoints must be monitored in neurothrombectomy device studies?
Monitor vessel perforation/dissection, hemorrhage, thrombus formation, neurologic deterioration (NIHSS change ≥4 points), re-occlusion, death, and device deployment failures. Document all adverse events regardless of device relationship.
What animal testing is recommended for neurothrombectomy devices?
Evaluate usability (maneuverability/flexibility), safety (vessel wall integrity, hemorrhagic/thrombogenic potential), and effectiveness (clot capture/destruction of variable compositions) in appropriate animal models with comparable vessel sizes.
How should revascularization success be defined and measured?
Define success as TIMI grade II or III flow establishment on post-procedure angiography. Use independent radiologist review for TIMI grading. Include collateral flow assessment as it’s an important clinical outcome predictor.
What are the primary effectiveness endpoints for neurothrombectomy studies?
Use validated neurologic scales (mRS, NIHSS, Barthel Index, Glasgow Outcome Scale) at 30 and 90 days. Define success as significantly increased good outcomes (mRS 0-2) versus controls or equivalent outcomes to other efficacious treatments.
What You Need to Do 👇
Recommended Actions
- Determine appropriate regulatory pathway (510(k), de novo, or PMA)
- Conduct comprehensive biocompatibility testing
- Perform bench testing to evaluate device mechanical properties
- Complete animal studies to assess usability, safety and effectiveness
- Design and conduct clinical study with:
- Clear inclusion/exclusion criteria
- Appropriate control group
- Comprehensive initial and follow-up assessments
- Well-defined safety and effectiveness endpoints
- Document all adverse events and outcomes thoroughly
- Consider consulting with FDA’s General Surgery Devices Branch for study design
- Ensure independent review of imaging and clinical assessments
- Validate any surrogate endpoints used in the study
Key Considerations
Clinical testing
- Subject selection criteria including inclusion/exclusion criteria
- Treatment window within 8 hours of symptom onset
- Initial assessments: angiography, imaging (CT/MRI), neurological evaluation (NIHSS)
- Follow-up assessments at multiple timepoints up to 90 days
- Primary endpoints for safety and effectiveness
- Clinical outcomes using validated neurologic scales (mRS, NIHSS, Barthel Index)
Non-clinical testing
- Bench testing to evaluate:
- Maneuverability
- Flexibility
- Durability
- Torque strength
- Establish device failure endpoints
Biocompatibility
- Testing according to ISO 10993-1 based on duration and level of contact
- For 510(k), can reference predicate device if identical materials and processing
Safety
- Evaluate hemorrhagic and thrombogenic potential
- Monitor vessel wall integrity
- Assess tissue damage potential
- Monitor temperature changes for energy-emitting devices
- Document all adverse events regardless of device relation
- Categorize severity of adverse events
Other considerations
- Animal testing to evaluate:
- Device usability in comparable vessels
- Safety aspects
- Effectiveness in capturing/destroying thrombi
- Revascularization success
Relevant Guidances 🔗
- Use of ISO 10993-1 for Biological Evaluation and Testing of Medical Devices
- Design Considerations for Medical Device Pivotal Clinical Studies
- Recommended Format and Content for Non-Clinical Bench Performance Testing in Medical Device Premarket Submissions
Related references and norms 📂
- ISO 10993-1: Biological Evaluation of Medical Devices Part 1: Evaluation and Testing