Clinical Study Design for Cardiac Ablation Systems in Treatment of Ventricular Tachycardia
This guidance provides recommendations for clinical study design to evaluate the safety and effectiveness of cardiac ablation systems for treating Ventricular Tachycardia (VT). It outlines both non-randomized and randomized study design options, focusing on specific considerations for different patient populations (ischemic VT vs. idiopathic VT).
What You Need to Know? 👇
What are the key differences between randomized and non-randomized study designs for VT ablation devices?
Non-randomized studies use patients as their own controls, comparing pre- and post-ablation VT episodes. Randomized studies compare treatment groups against concurrent controls, either market-approved ablation systems or drugs, requiring larger sample sizes but providing stronger evidence.
How should VT episodes be counted and documented in clinical studies?
Use consistent methods pre- and post-ablation including ICD interrogation, event monitoring, and hospital ECGs. Count only VT episodes >20 seconds duration or sufficient to trigger therapy. Avoid patient self-reporting and retrospective assessments to minimize bias.
What constitutes “acute success” versus “6-month success” in VT ablation studies?
Acute success is defined as non-inducibility of clinically relevant VT morphologies immediately post-procedure. 6-month success is either reduction in VT episodes or absence of VT episodes during follow-up, depending on patient population and study design.
When should ischemic VT patients versus idiopathic VT patients be enrolled differently?
Ischemic VT patients are suitable for non-randomized studies with “reduction in VT episodes” as the endpoint. Idiopathic VT patients should preferably be enrolled in randomized studies with “absence of VT” as the endpoint due to less established ablation benefits.
What are the requirements for major complication reporting in VT ablation studies?
Major complications include life-threatening events, permanent impairment, events requiring significant intervention, hospitalization, moderate transient impairment, or requiring intervention like medication/cardioversion. All must occur within the first week post-procedure and be clearly documented.
How should repeat ablations and crossovers be handled in VT ablation clinical studies?
Repeat ablations are allowed after patients are categorized as 6-month failures, maintaining study integrity. In randomized studies, crossovers should occur only after completing 6-month follow-up (Option 2) or after failure classification (Option 1).
What You Need to Do 👇
Recommended Actions
- Define study design type (randomized or non-randomized) based on intended claims and patient population
- Establish clear inclusion/exclusion criteria, particularly regarding VT frequency and ICD requirements
- Define primary endpoints including acute success, 6-month success, and complication rates
- Develop detailed protocol for VT episode documentation
- Implement required pre and post-ablation procedures
- Establish statistical analysis plan according to chosen study design
- Create clear criteria for repeat ablations and/or crossovers
- Develop comprehensive adverse event monitoring system
- Establish consistent documentation methods for VT episodes
- Create detailed follow-up schedule and procedures
Key Considerations
Clinical testing
- Two study design options: non-randomized (single-arm) and randomized (concurrent control)
- 6-month follow-up period required
- Primary endpoints must include acute success rate, 6-month success rate, and complication rate
- Pre and post-ablation procedures including echocardiogram and neurologic examination
- VT episode documentation through ICD interrogation, event monitoring, or ECG
- Baseline data collection for 6 months prior to ablation in non-randomized studies
Labelling
- Success criteria and endpoints must be clearly defined
- Consistency in offering repeat ablations should be maintained for labeling purposes
Safety
- Major complications must be documented within the first week post-procedure
- Complications should be stratified between acute (within first week) and later occurrences
- Clear definition of major vs. minor complications provided in guidance
Other considerations
- Patient selection criteria must be clearly defined
- Statistical analysis requirements for both study designs
- Specific considerations for repeat ablations and crossovers
- Different success criteria for ischemic vs. idiopathic VT patients