ASpirin as a treatment for ARDS (STAR)

: A phase 2 randomised controlled trial

Abstract

Rationale:
Acute respiratory distress syndrome (ARDS) remains a common cause of significant mortality and morbidity for which there is currently no pharmacological treatment. Platelets play an important role in the pathophysiology of ARDS. There is in vivo, in vitro, observational and clinically relevant phase I evidence suggesting that aspirin may be of benefit in the treatment of ARDS.

Objectives:
The aim of the STAR trial (aSpirin as a Treatment for ARDS) was to test the hypothesis that enteral aspirin 75mg was both safe and effective in improving important surrogate outcomes in adult patients with ARDS.

Methods:
This randomised, double blind (patient and investigator), allocation concealed, placebo-controlled phase 2 trial was conducted in five intensive care units. Patients fulfilling the 2012- updated American- European Consensus Conference definition of ARDS (Berlin Definition) were randomly assigned in a 1:1 ratio to receive enteral aspirin 75mg or placebo for a maximum of 14 days using a computer-generated randomisation schedule with variable block size stratified by vasopressor requirement. The primary endpoint was oxygenation index at day 7. Secondary outcomes included respiratory compliance (Crs), PaO2/FiO2 ratio, change in sequential organ failure assessment (SOFA) score and safety parameters. Analyses were by intention to treat.

Measurements and Main Results:
The trial was stopped early after 49 of a planned 60 patients were recruited due to slow recruitment, with 24 patients allocated to aspirin and 25 patients allocated to placebo. There was no significant difference in oxygenation index at day 7 (unadjusted mean 54.4 [SD 26.8] in aspirin group, 42.4 [SD 25] in placebo group; mean difference 12.0, 95% CI -6.1 to 30.1, p= 0.19). Furthermore, aspirin did not have a significant impact on any of the secondary outcomes. However, the administration of aspirin in critically ill adult patients with ARDS was well tolerated with no difference in the number of adverse events (13 events in both groups; odds ratio 1.04, 95% CI 0.56 to 1.94, p=0.56).

Conclusion:
Aspirin was well tolerated but did not improve oxygenation index or other physiological outcomes in adult patients with ARDS.

Date of Award	Jul 2021
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Health and Social Care (Northern Ireland) Research and Development
Supervisor	Danny McAuley (Supervisor) & Cecilia O'Kane (Supervisor)