Acetylsalicylic Acid Treatment in Patients With Sepsis and Septic Shock: A Phase 2, Placebo-Controlled, Randomized Clinical Trial.

Summary

In a multicenter, blinded, placebo-controlled RCT (n=166), 7 days of 200 mg/day aspirin did not improve SOFA score change in adults with early sepsis and increased major bleeding and serious adverse events, prompting early termination. Secondary outcomes were also negative.

Key Findings

• No significant difference in SOFA score change between aspirin and placebo (adjusted mean difference 0.60; 95% CI −0.55 to 1.75; p=0.30).
• Higher major bleeding in aspirin group (8/94 [8.5%] vs 1/84 [1.2%]; p=0.02) and more serious adverse events (9 [11%] vs 1 [1.2%]; p=0.009).
• Trial stopped early after interim safety analysis due to bleeding signal; secondary outcomes showed no benefit.

Clinical Implications

Do not initiate aspirin solely to attenuate organ dysfunction in sepsis; carefully reassess continuation of prior aspirin therapy in the acute phase considering bleeding risk. Antiplatelet strategies in sepsis require caution and should be evaluated within trials.

Limitations

• Early termination reduced statistical power for some efficacy endpoints and limits precision.
• Conducted in five ICUs in Brazil; generalizability to other settings and to patients with chronic antiplatelet use requires further study.

Future Directions

Identify subgroups where antiplatelet modulation may be beneficial, compare alternative platelet-targeting strategies with better safety profiles, and evaluate timing relative to sepsis trajectory.