Original Investigation
Caring for the Critically Ill Patient
June 14, 2016

Effect of Aspirin on Development of ARDS in At-Risk Patients Presenting to the Emergency DepartmentThe LIPS-A Randomized Clinical Trial

Author Affiliations
  • 1Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota
  • 2Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota
  • 3Department of Surgery, University of Michigan School of Medicine, Ann Arbor
  • 4Department of Medicine, Mayo Clinic College of Medicine, Jacksonville, Florida
  • 5Beth Israel Deaconess Medical Center, Boston, Massachusetts
  • 6Department of Anaesthesia, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
  • 7Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota
  • 8Department of Medicine and Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 9Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee
  • 10Department of Medicine, Albert Einstein College of Medicine, Bronx, New York

Copyright 2016 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

JAMA. 2016;315(22):2406-2414. doi:10.1001/jama.2016.6330

Importance  Management of acute respiratory distress syndrome (ARDS) remains largely supportive. Whether early intervention can prevent development of ARDS remains unclear.

Objective  To evaluate the efficacy and safety of early aspirin administration for the prevention of ARDS.

Design, Setting, and Participants  A multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 16 US academic hospitals. Between January 2, 2012, and November 17, 2014, 7673 patients at risk for ARDS (Lung Injury Prediction Score ≥4) in the emergency department were screened and 400 were randomized. Ten patients were excluded, leaving 390 in the final modified intention-to-treat analysis cohort.

Interventions  Administration of aspirin, 325-mg loading dose followed by 81 mg/d (n = 195) or placebo (n = 195) within 24 hours of emergency department presentation and continued to hospital day 7, discharge, or death.

Main Outcomes and Measures  The primary outcome was the development of ARDS by study day 7. Secondary measures included ventilator-free days, hospital and intensive care unit length of stay, 28-day and 1-year survival, and change in serum biomarkers associated with ARDS. A final α level of .0737 (α = .10 overall) was required for statistical significance of the primary outcome.

Results  Among 390 analyzed patients (median age, 57 years; 187 [48%] women), the median (IQR) hospital length of stay was 6 3-10) days. Administration of aspirin, compared with placebo, did not significantly reduce the incidence of ARDS at 7 days (10.3% vs 8.7%, respectively; odds ratio, 1.24 [92.6% CI, 0.67 to 2.31], P = .53). No significant differences were seen in secondary outcomes: ventilator-free to day 28, mean (SD), 24.9 (7.4) days vs 25.2 (7.0) days (mean [90% CI] difference, −0.26 [−1.46 to 0.94] days; P = .72); ICU length of stay, mean (SD), 5.2 (7.0) days vs 5.4 (7.0) days (mean [90% CI] difference, −0.16 [−1.75 to 1.43] days; P = .87); hospital length of stay, mean (SD), 8.8 (10.3) days vs 9.0 (9.9) days (mean [90% CI] difference, −0.27 [−1.96 to 1.42] days; P = .79); or 28-day survival, 90% vs 90% (hazard ratio [90% CI], 1.03 [0.60 to 1.79]; P = .92) or 1-year survival, 73% vs 75% (hazard ratio [90% CI], 1.06 [0.75 to 1.50]; P = .79). Bleeding-related adverse events were infrequent in both groups (aspirin vs placebo, 5.6% vs 2.6%; odds ratio [90% CI], 2.27 [0.92 to 5.61]; P = .13).

Conclusions and Relevance  Among at-risk patients presenting to the ED, the use of aspirin compared with placebo did not reduce the risk of ARDS at 7 days. The findings of this phase 2b trial do not support continuation to a larger phase 3 trial.

Trial Registration  clinicaltrials.gov Identifier: NCT01504867