1. FDA Pathway to Approval: Clinical Requirements for Renal Denervation
Todd Courtney, MS
Peripheral Interventional Devices Branch
Division of Cardiovascular Devices
Food and Drug Administration

2. Current Regulatory Status
There are no cardiovascular devices approved for renal denervation.

3. Pre-Clinical Testing Animal Testing Bench testing
Acute/Chronic
Assess proof of concept for therapy
Bench testing
Use risk analysis to develop engineering tests
Consider worst case scenario
Biocompatibility, EMC/EMT, etc.

4. Patient Population Patients should have refractory hypertension.
Systolic blood pressure ≥160 mmHg (≥150 mmHg for type 2 diabetics)
Adhering to a stable drug regimen of 3 or more anti-hypertensive medications (including 1 diuretic)
ABPM should be used to rule out ‘white coat’ hypertension
No renal artery stenosis or anatomy that would be ineligible for treatment

5. Patient Population
Blood pressure measurement should be objective for entry and baseline.
Same devices and protocols to measure SBP/DBP
There should be a run-in period to ensure patient is refractory.
2 weeks of blood pressure and medication monitoring
Confirmation of refractory hypertension
Office SBP > 160 mmHg
Ambulatory blood pressure monitoring
Medication compliance

6. Primary Endpoints Effectiveness: Improvement in blood pressure (6 mo)
Systolic as primary endpoint
Should be clinically meaningful, not just a statistically significant decrease as compared to a control or performance goal
Reduction should be sustained.
Safety: MAE compared to other renal interventions at 6 mo.
MAE based on literature rates of renal interventions
Death, stroke, MI, perforation, dissection, etc.
Study should be powered for both safety and effectiveness

7. Secondary Analyses Important because first device will go to panel
Secondary analyses should investigate
How patients fare depending on entry blood pressure
Reduction in medications
Treatment number of medications
DBP improvement
Correlation of ambulatory and office-based BP

8. Important Considerations
First-in-Man study important to assess proof of concept
Prefer a randomized trial, because there isn’t robust control data.
Follow-up at 1, 3, 6, 9, 12 months for year 1; every 6 months thereafter.
Long term follow-up to assess sustainablility of treatment effect.
Post-market study to assess effect of therapy on broader population

9. Other Considerations Early Feasibility Study Presubmission program
Allows for early clinical evaluation of devices to provide proof of principle and initial clinical safety data.
Appropriate early in device development when clinical experience is necessary because nonclinical testing methods are not available or adequate to provide the information needed to advance the developmental process.
Presubmission program
Old pre-IDE submission process

10. Todd Courtney todd.courtney@fda.hhs.gov 301-796-6371
Thank You!
Todd Courtney