title: Effect of Aspirin on Development of ARDS in At-Risk Patients Presenting to the Emergency Department: The LIPS-A Randomized Clinical Trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  Among 390 analyzed patients (median age, 57 years; 187 [48%] women), 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 (OR, 1.24; 92.6%CI, 0.67-2.31). No significant differences were seen in secondary outcomes or adverse events. [table: see text]
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01504867.
authors.affiliation: Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Daryl J
authors.initials: DJ
authors.lastname: Kor
authors.affiliation: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Rickey E
authors.initials: RE
authors.lastname: Carter
authors.affiliation: Department of Surgery, University of Michigan School of Medicine, Ann Arbor.
authors.forename: Pauline K
authors.initials: PK
authors.lastname: Park
authors.affiliation: Department of Medicine, Mayo Clinic College of Medicine, Jacksonville, Florida.
authors.forename: Emir
authors.initials: E
authors.lastname: Festic
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Valerie M
authors.initials: VM
authors.lastname: Banner-Goodspeed
authors.affiliation: Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Richard
authors.initials: R
authors.lastname: Hinds
authors.affiliation: Department of Anaesthesia, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Daniel
authors.initials: D
authors.lastname: Talmor
authors.affiliation: Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota.
authors.forename: Ognjen
authors.initials: O
authors.lastname: Gajic
authors.affiliation: Department of Medicine and Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee9Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Lorraine B
authors.initials: LB
authors.lastname: Ware
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Michelle Ng
authors.initials: MN
authors.lastname: Gong
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D004311:Double-Blind Method; D004636:Emergency Service, Hospital; D005260:Female; D006801:Humans; D015994:Incidence; D057194:Intention to Treat Analysis; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D012128:Respiratory Distress Syndrome / Q000453:epidemiology / Q000517:prevention & control*; D013997:Time Factors; D014481:United States
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001241:Aspirin