Aspirin to Reduce the Risk of Thrombotic Events in Patients With End-Stage Renal Disease: Protocol for a Randomized Controlled Trial (Preprint)

Abstract

Results: we developed a protocol for a phase II randomized, single-center, placebocontrolled, triple-blind, superiority clinical trial in order to assess aspirin prophylactic efficacy and safety in ESRD patients on hemodialysis. It follows the ethical principles of the Declaration of Helsinki of the World Medical Association. Participants will be randomized (1:1 ratio) in 2 arms and orally receive acetylsalicylic acid 100mg/day or placebo, for 12 months. An intent-to-treat (ITT) statistical analysis will be performed.The primary composite outcome (12-month incidence of thrombotic events [cardiac death, nonfatal myocardial infarction, nonfatal stroke, arteriovenous fistula thrombosis] and TIMI major bleeding) will be analyzed with Kaplan Meier curves and a log-rank test to compare treatment arms. Cox proportional hazards regression will be used to adjust for covariates, if appropriate. As secondary outcomes, the same components of the primary outcome will be assessed in a subgroup analysis after patients' stratification for the presence versus absence of type-2 Diabetes Mellitus and platelet hyper-reactivity. The presence of TIMI minor bleeding will be compared between groups and tested with a Chi-square test. Conclusions:We provide a protocol for a randomized controlled trial to evaluate aspirin's prophylactic efficacy for thrombotic events and safety in ESRD patients.When conducted, such a study would further our understanding of the mechanism of aspirin-related bleeding, and would help identify best-responders and patients with a higher risk of adverse events.