Aspirin for Sepsis Flops in Trial

ORLANDO — Aspirin failed to cut the intensity of organ dysfunction in patients with sepsis, a placebo-controlled phase II trial from Brazil showed.

For the primary endpoint — mean change in Sequential Organ Failure Assessment (SOFA) score between day 0 and 7 or the day of discharge/death — there was no significant difference between groups, with a decrease of 1.37 with aspirin and 0.73 with placebo (adjusted difference 0.60, 95% CI -0.55 to 1.75, P=0.30).

Yet aspirin “increased the risk of severe bleeding compared to placebo,” said Thiago Miranda Lopes de Almeida, PhD, of Hospital São Paulo in Brazil, in a presentation here at the Society of Critical Care Medicine annual meeting.

There were also no significant differences in secondary and tertiary outcomes, including mechanical ventilation-free days (median 13 for both groups) or death (32% vs 36% for the aspirin and placebo groups, respectively) at 28 days, or for new organ dysfunction (74% vs 71%).

Results of the 166-patient trial were published simultaneously in Critical Care Medicine.

Ken Tegtmeyer, MD, of Cincinnati Children’s Hospital Medical Center, who was not involved in the study, said the findings clearly show that this protocol of aspirin “was not effective in treatment of sepsis.”

However, Tegtmeyer said it’s not necessarily time to call it quits for investigating aspirin in this setting. “This was a small study,” he told MedPage Today. “The use of 200 mg of aspirin daily may have been too large for these patients. I believe there will be other trials that use aspirin in this area. The book isn’t closed yet.”

As aspirin has anti-inflammatory and antiplatelet activity, the researchers had hypothesized that aspirin could prevent or reduce certain sepsis characteristics (inflammatory dysregulation, microcirculation derangement, endothelium activation, platelet aggregation, micro-thrombosis) and potentially counter hypoperfusion and organ dysfunction, Almeida explained.

The phase II ASP-SEPSIS trial was conducted at five intensive care units in Brazil in 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; partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO₂/FiO₂) ratio <200; or septic shock. Participants were randomized to receive aspirin (200 mg) or placebo daily for 7 days.

Median age was 57-61 years, and 52% were men. About half were hospitalized due to COVID-19, and community-acquired pneumonia was the type of infection for more than three-fourths. At baseline, 62% of the aspirin group and 67% of the placebo group had septic shock, while the median SOFA score was 7 and 6, respectively.

The researchers had hypothesized that from a mean baseline SOFA of 8.8, standard therapy would reduce that score by at least 2 points, while aspirin would lower the score by at least 3 points, Almeida said. He also noted that the trial had planned to include 109 patients in each group, but the study was halted early because of the increase of bleeding events in the aspirin group.

Major bleeding occurred in 9.8% of the aspirin group versus 1.2% of the placebo group (P=0.02), Almeida reported. Of those, five patients on aspirin and one placebo patient required blood transfusions (P=0.11).

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