Post hoc Feasibility Analysis of a Randomized Controlled Trial Comparing Low-dose Aspirin for Preeclampsia Prevention: Implications for Future Trial Design

Abstract Background: While randomized controlled trials (RCTs) provide critical efficacy data, embedded feasibility analyses are essential for informing the design of larger definitive studies. Although our primary RCT demonstrated preliminary efficacy signals comparing 150 mg versus 75 mg aspirin for preeclampsia prevention, the feasibility of implementing such comparative dose studies in obstetric population remained incompletely characterized. Objective: The objective of this study was to conduct a comprehensive post hoc feasibility analysis of our completed RCT, evaluating key implementation metrics that inform the viability of larger-scale comparative aspirin dose investigations. Methods: We performed a post hoc analysis of feasibility parameters from our double-masked RCT conducted at AIIMS, Raipur (November 2021–November 2022), which randomized 100 high-risk pregnant women to 75 mg ( n = 48) versus 150 mg ( n = 52) daily aspirin. We retrospectively analyzed predefined feasibility metrics, including recruitment velocity, randomization acceptance rates, intervention adherence, participant retention, outcome assessment completeness, and protocol implementation success. These parameters were evaluated against established benchmarks for obstetric intervention trials. Results: Post hoc feasibility analysis revealed exceptional implementation success across all evaluated domains. Monthly recruitment averaged 8.3 participants (range: 6–12), exceeding typical single-center obstetric trial benchmarks. Randomization acceptance reached 84.7% (100/118 approached participants), demonstrating strong participant willingness to accept dose-comparison randomization. High adherence was observed across both treatment arms, with 94% of participants completing ≥80% of the intended dose. Retention rates were optimal (100% for maternal outcomes and 98% for neonatal outcomes). Complete outcome assessment protocols were successfully implemented with 99% of data completeness. Protocol deviations were minimal (8% minor and 2% major) with no impact on primary feasibility metrics. The embedded feasibility analysis indicates that a definitive, adequately powered trial would be highly feasible, requiring approximately 764 participants based on observed effect sizes (6.9% absolute difference in preeclampsia rates) and variance parameters. Conclusion: This post hoc feasibility analysis of our comparative aspirin dose RCT demonstrates exceptional implementation success, validating the viability of larger definitive trials. The robust recruitment, high acceptance rates, excellent adherence, and complete retention observed provide compelling evidence that multicenter comparative dose trials are feasible and should be prioritized. These findings offer critical implementation guidance for designing adequately powered definitive investigations in this clinically important area.