Trends and Predictors of Premature Termination of Cardiovascular Trials: A Systematic Review

Premature termination of cardiovascular trials undermines evidence generation and wastes resources.

The objective of the study was to evaluate trends, predictors, and recruitment adequacy among prematurely terminated cardiovascular trials.

We analyzed adult cardiovascular trials registered on ClinicalTrials.gov (2000-2025). Trial characteristics, early termination, and reported reasons were extracted. Computed low recruitment was defined as actual enrollment <80% of target. Multivariable logistic regression identified independent predictors of termination.

Among 19,191 trials, 2,202 (11.5%) were prematurely terminated. Low recruitment was the most common reported reason (946/2,202, 42.9%), yet 625/1,571 (39.9%) underenrolled trials did not report recruitment failure. Termination peaked in 2020 (155/1,033, 15.0%). Termination risk was the highest in early-phase trials (phases 1/2 or 2; 371/2,325, 16.0%) and lowest for behavioral/lifestyle interventions (146/2,998, 4.9%) and female-only trials (23/475, 4.8%). In multivariable analysis, small sample size (1-100 participants; OR: 3.37; 95% CI: 2.98-3.80) and later-phase trials (phase 2/3 or 3; OR: 1.69; 95% CI: 1.41-1.97) were associated with higher odds of termination, whereas behavioral/lifestyle interventions (OR: 0.40; 95% CI: 0.32-0.49), crossover designs (OR: 0.53; 95% CI: 0.42-0.65), and non-U.S. government funding (OR: 0.50; 95% CI: 0.31-0.78) were protective.

More than 1 in 10 cardiovascular trials terminate early, most often due to poor recruitment, which is frequently under-reported. Improved feasibility assessment and transparent reporting are needed. (Trends and Predictors of Premature Termination of Cardiovascular Trials: A Systematic Review; CRD420251155096).