Applying Exercise Capacity and Physical Activity as Single vs Composite Endpoints for Trials of Cardiac...

Area of Science:

• Cardiology
• Clinical Trials
• Rehabilitation Medicine

Background:

• Cardiac rehabilitation (CR) interventions aim to improve patient outcomes.
• Exercise capacity and physical activity are key indicators for reduced mortality in cardiac patients.
• Current primary endpoints in CR trials may not fully capture treatment effects.

Purpose of the Study:

• To develop a composite primary endpoint (CE) for exercise-based CR randomized controlled trials (RCTs).
• To assess the statistical efficiency and sample size requirements of this novel CE.
• To explore the application of the CE in parallel-group RCTs.

Main Methods:

• A composite endpoint was conceptualized by combining exercise capacity and physical activity measures.
• Statistical exploration of sample size requirements was conducted.
• Sample size needs for the CE were compared against single endpoints using data from two CR trials.

Main Results:

• The CE combines dichotomous measures of achieved exercise capacity and physical activity.
• Depending on baseline proportions and intervention aims, the CE can either increase or decrease required sample sizes.
• Reductions in sample size of up to 55% or 70% were observed in specific scenarios.

Conclusions:

• The composite endpoint offers a potential strategy to optimize sample size in exercise-based CR trials.
• Trialists should carefully consider baseline characteristics and intervention goals when implementing the CE.
• The CE's utility in reducing sample size is context-dependent, requiring careful evaluation.