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Clinical Study Design Recommendations for Catheter Ablation Devices in Treatment of Type I Atrial Flutter

This guidance addresses clinical study designs for catheter ablation devices specifically intended for the treatment of type I atrial flutter (cavotricuspid dependent, right atrial macro-reentrant arrhythmia). It applies to class III devices requiring PMA approval under product code OAD.

What You Need to Know? 👇

What are the key clinical study design requirements for catheter ablation devices treating atrial flutter?

FDA recommends randomized controlled trials (RCTs) as the least burdensome approach. Alternative designs like single-arm trials with performance goals are acceptable if scientifically justified, but require higher quality data standards.

What should be the primary effectiveness endpoint for atrial flutter ablation device studies?

The primary endpoint should be chronic success, defined as absence of recurrent atrial flutter at 6 months post-ablation. For qualified RF catheters, acute procedural success (bidirectional conduction block) may serve as surrogate.

Which safety events must be included in the composite safety endpoint for ablation studies?

The composite must include cardiac perforation/tamponade, cerebrovascular accident, complete heart block, death, myocardial infarction, pulmonary embolism, transient ischemic attack, and device-specific risks. Monitor for 7 days post-procedure.

What are the essential inclusion and exclusion criteria for atrial flutter ablation studies?

Include patients with documented Type I atrial flutter requiring ablation. Exclude those with prior isthmus ablation, inability to stop anti-arrhythmic drugs, recent MI, intracardiac thrombus, or significant comorbidities affecting safety evaluation.

How long should follow-up monitoring continue for atrial flutter ablation device studies?

Minimum follow-up includes telephone contact at 7 days, outpatient visits at 30 days and 6 months. Use standardized protocols with symptom documentation, 12-lead ECG, and event monitoring for suspected recurrences.

What anticoagulation requirements apply to atrial flutter ablation clinical studies?

Patients likely in atrial flutter during ablation need 3-4 weeks pre-procedural anticoagulation (or TEE showing no thrombus) and 3-4 weeks post-procedural therapeutic anticoagulation, following atrial fibrillation guidelines.


What You Need to Do 👇

  1. Design a randomized controlled trial unless strong justification exists for alternative design
  2. Develop clear inclusion/exclusion criteria based on guidance suggestions
  3. Establish primary effectiveness endpoint (chronic or acute success based on device characteristics)
  4. Define composite safety endpoint including all required adverse events
  5. Create standardized monitoring protocol with specified follow-up schedule
  6. Develop anticoagulation protocol aligned with guidance recommendations
  7. Select qualified investigators with appropriate training
  8. Establish comprehensive study monitoring plan
  9. Design focused data collection forms
  10. Pre-specify all statistical analyses and sample size calculations
  11. Implement independent clinical events committee for adverse event evaluation

Key Considerations

Clinical testing

  • Randomized Controlled Trials (RCTs) are recommended as the preferred study design
  • Primary effectiveness endpoint should be chronic success (absence of recurrent atrial flutter at 6 months)
  • For select catheters, acute procedural success (bidirectional block at cavo-tricuspid isthmus) may serve as surrogate endpoint
  • Follow-up visits recommended at 7 days, 30 days and 6 months
  • Study subjects should be monitored through symptoms documentation and cardiac rhythm assessment

Safety

  • Composite serious adverse event endpoint required including:
    • Cardiac perforation/tamponade
    • Cerebrovascular accident
    • Complete heart block
    • Death
    • Myocardial infarction
    • Pulmonary embolism
    • Transient ischemic attack
  • Safety assessment period of 7 days post-ablation
  • Independent clinical events committee required for adverse events evaluation

Other considerations

  • Anticoagulation requirements:
    • 3-4 weeks therapeutic anticoagulation pre-procedure if patient in atrial flutter
    • 3-4 weeks post-procedure anticoagulation for patients in atrial flutter
  • Investigator selection based on training and clinical experience
  • Comprehensive monitoring plan required
  • Statistical considerations must be pre-specified in protocol

Relevant Guidances 🔗

  • 21 CFR 812: Investigational Device Exemptions
  • 21 CFR 56: Institutional Review Boards
  • 21 CFR 50: Protection of Human Subjects
  • 21 CFR 814.15: Research Conducted Outside the United States

Original guidance

  • Clinical Study Design Recommendations for Catheter Ablation Devices in Treatment of Type I Atrial Flutter
  • HTML / PDF
  • Issue date: 2008-08-05
  • Last changed date: 2020-03-24
  • Status: FINAL
  • Official FDA topics: Medical Devices, Premarket, Good Clinical Practice (GCP)
  • ReguVirta ID: b483bdfb03e6ac3fe9df99a181ccdb35
This post is licensed under CC BY 4.0 by the author.