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

OBJECTIVES: Platelets play a critical role in the inflammatory response and coagulation. We aimed to evaluate whether the use of acetylsalicylic acid (ASA) would reduce the intensity of organ dysfunction in septic patients. DESIGN: Randomized, blinded, parallel-group, placebo-controlled trial. SETTING: Five general ICUs in Brazil. PATIENTS: Adults with sepsis for no longer than 48 hours who had at least one severe organ dysfunction (lactate > 4 mmol/L, platelets < 100,000/mm3, Pao2/Fio2 ratio < 200, or septic shock). INTERVENTIONS: Patients were randomized to receive 200 mg of ASA or placebo for 7 days. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the change in the Sequential Organ Failure Assessment (SOFA) score between day 0 and day 7 or date of discharge/death. Safety outcomes were major bleeding and the number of blood transfusions within 14 days. The planned sample size was 218 with interim safety analyses after enrolling 109 and 163 patients. The study was discontinued due to higher frequency of major bleeding in the ASA group. We included 166 patients (ASA: 82 patients, placebo: 84). In the adjusted analysis, there was no difference in the SOFA change between the groups (mean placebo to ASA group difference, 0.60; 95% CI, -0.55 to 1.75; p = 0.30). There were no differences in any of the secondary outcomes. In the intervention group, there were a higher number of serious adverse events (9 [11%] vs. 1 [1.2%]; p = 0.009) and major bleeding (8 [8.5%] vs. 1 [1.2%]; p = 0.02). CONCLUSIONS: In this population of septic patients, ASA did not reduce the intensity of organ dysfunction. ASA increased the risk of severe bleeding compared with placebo.