ASPIrin to Reduce Events in Dialysis (ASPIRED) trial: a pragmatic, registry-based, double-blind randomized clinical trial

Individuals with kidney failure receiving dialysis have a substantially greater risk of suffering cardiovascular (CV) events than the age- and gender-matched general population. Although aspirin is an effective antiplatelet agent commonly used for primary and secondary CV prevention, data regarding its role in the dialysis population is limited to a few post hoc analyses of larger trials, partly due to the paradoxical relationship between thromboembolic and bleeding risk in patients on dialysis. Here, we report the trial design and recruitment status of an adequately powered, pragmatic, registry-based, double blind, randomised controlled trial aiming to determine the efficacy and safety of low dose aspirin versus placebo in reducing CV events and mortality in patients on maintenance hemodialysis (HD) or peritoneal dialysis (PD) (NCT04381143).

ASPIRED is a multicentre, investigator-initiated, collaborative study jointly designed by the Guangdong People Provincial Hospital (GDPH) and the George Institute for Global Health (TGI). Eligible participants are pre-identified from the Chinese Dialysis Registry (n~29,000) with broad inclusion criteria i.e. prevalent or incident adults (≥18 years old) on maintenance HD or PD who are able to provide informed consent. Individuals with aspirin intolerance or an indication for antiplatelet/ anticoagulation therapy, recent intracranial bleed, or deemed not suitable by treating clinicians, are excluded. Consenting participants are randomised to either oral aspirin 100mg daily or matched placebo in a 1:1 ratio stratified by centre, dialysis modality, a history of CV disease and presence of diabetes mellitus. The primary endpoint is the composite of major adverse cardiovascular events (MACE), defined as the first occurrence of myocardial infarction, ischemic stroke or death from CV causes. Secondary endpoints include a composite of MACE and all-cause death, hospitalised unstable angina and transient ischaemic attack, the individual components of the primary composite, all-cause mortality, coronary revascularisation, fistula or graft thrombosis, intracranial haemorrhage, and ischaemic events. The main safety endpoint is major bleeding. A sample size of 9000 participants is estimated to give 90% power to detect an 18.5% relative risk reduction with low dose aspirin versus placebo, based on an estimated 1011 primary events. This event-based trial utilises an intention to treat analysis with three protocol-specified interim analyses planned using Haybittle-Peto efficacy boundaries. The trial Steering Committee is responsible for the overall trial conducts, and a Data Safety Monitoring Committee provides ongoing independent review of trial safety parameters.

The study is ongoing with 8118 participants randomized in Oct 2025 from 107 centers in China. Approximately 2/3 are male with a similar proportion receiving HD. Two protocol specified interim analyses were completed to date and the DMSC has advised continuation of the trial.

To date, ASPIRED trial is the largest definitive trial of aspirin vs placebo in patients receiving dialysis, and will provide much-needed evidence regarding benefits in preventing CV events and mortality, as well as any risks. Irrespective of the outcome, the results of the ASPIRED trial will be impactful and likely to change clinical practice.