Abstract TP11: Acute Stroke Randomized Clinical Trials: What Factors Help Trials Achieve Their Intended Sample Size?

Abstract

Background: We performed a systematic review of acute stroke trials to determine features associated with premature termination of trial enrollment. Methods: MEDLINE was searched for stroke RCTs between 1/1/2013-6/11/2020. Included studies were Phase 2 or 3, had a preplanned sample size ≥100, had time to treatment within 24 hours of onset for TIA, ischemic stroke, or ICH, and were published in a major clinical journal (BMJ, Circulation, Stroke, Neurology, JAMA, JAMA Neurology, Lancet, Lancet Neurology, NEJM). Studies were deemed prematurely terminated if authors reported early termination. Study variables and inclusion criteria are listed in Table 1. Complex trials required specialized training and expertise, high degree of monitoring, or procedural intervention. Univariate Chi-square tests/Fisher’s exact test were used to determine characteristics associated with early termination, and multivariable lasso logistic regression was used to select the most important predictors. Results: Of 1,219 studies assessed, 69 trials met eligibility criteria for inclusion (Table 1); 34 (49%) were prematurely terminated. In univariate analysis, variables associated with premature termination were complexity of treatment, industry involvement, exclusion of older patients, and presence of a futility stopping rule. In lasso regression, complex treatment trials (OR 3.77, 95% CI 1.30-10.97, versus moderate or simple trials combined), presence of a futility rule (OR 3.56, 95% CI 1.02-12.40 versus no rule), and geographic region (North America OR 1.97, 95% CI 0.57-6.81 versus all other regions combined) were selected as important factors. Conclusion: Half of acute stroke trials were terminated prematurely. Broadening inclusion/exclusion criteria and simplifying the complexity of trials may decrease the likelihood of unplanned premature termination, whereas planned futility analyses may appropriately terminate trials early, saving money and resources.