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

• Published in: JAMA : the journal of the American Medical Association Vol. 315; no. 22; pp. 2406 - 2414
• Main Authors: Kor, Daryl J, Carter, Rickey E, Park, Pauline K, Festic, Emir, Banner-Goodspeed, Valerie M, Hinds, Richard, Talmor, Daniel, Gajic, Ognjen, Ware, Lorraine B, Gong, Michelle Ng
• Format: Journal Article
• Language: English
• Published: United States American Medical Association 14-06-2016
• Subjects: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Aspirin; Aspirin - therapeutic use; Clinical trials; Double-Blind Method; Emergency Service, Hospital; Female; Humans; Incidence; Intention to Treat Analysis; Length of Stay; Male; Middle Aged; Patients; Respiratory Distress Syndrome - epidemiology; Respiratory Distress Syndrome - prevention & control; Time Factors; United States; United States
• ISSN: 0098-7484; 1538-3598
• 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