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LIPS-A: Lung Injury Prevention Study With Aspirin

Phase 2
Completed
Conditions
Acute Respiratory Distress Syndrome
Interventions
Registration Number
NCT01504867
Lead Sponsor
Mayo Clinic
Brief Summary

The primary hypothesis was that early aspirin administration will decrease the rate of developing acute lung injury during the first 7 days after presentation to the hospital.

Detailed Description

Acute respiratory distress syndrome (ARDS) remains a life-threatening critical care syndrome characterized by alveolar-capillary membrane injury and hypoxemic respiratory failure. The median time to onset of ARDS is 2 days after hospital presentation. Therefore, the period between hospital presentation and the development of ARDS presents a brief window of opportunity for ARDS prevention.

This was a multicenter, double-blind, placebo-controlled, parallel-group, Phase 2b, randomized clinical trial. Development of ARDS was defined by Berlin criteria (modified to require invasive mechanical ventilation) within 7 days of hospital admission. The first dose of study drug or placebo was administered within 24 hours after presentation to the hospital. Important co-interventions were standardized across sites using a web-based tool, Checklist for Lung Injury Prevention. Study participants were screened daily for receipt of mechanical ventilation and determination of the partial pressure of arterial oxygen (PaO2) or oxygen saturation to fraction of inspired oxygen ratio (SpO2:FIO2). If the participant's SpO2:FIO2 ratio was consistently below 315, hypoxemia was confirmed with measurement of arterial blood gas. Chest radiographs for all intubated patients with a SpO2:FIO2 of 300 or less were independently reviewed by both site investigator and a member of the trial's executive committee. Study participants who died or were discharged from the hospital before day 7 without meeting criteria for ARDS were adjudicated as not having ARDS.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
400
Inclusion Criteria
  • Adult patients (age > 18) admitted to the hospital through the emergency department (ED)
  • At high risk of developing acute lung injury (ALI) Lung Injury Prediction Score (LIPS) greater than or equal to 4
Exclusion Criteria
  • Anti-platelet therapy on admission or within 7 days prior to admission
  • Presented to outside hospital ED > 12 hrs before arrival at site's facility
  • Inability to obtain consent within 12 hours of hospital presentation
  • Admitted for elective surgery
  • Acute lung injury prior to randomization
  • Receiving mechanical ventilation through a tracheostomy tube prior to current hospital admission (patient who is ventilator dependent)
  • Presence of bilateral pulmonary infiltrates on admission if he or she has a history of bilateral pulmonary infiltrates (as evidenced by previous x-rays) that can reasonably explain the current degree of pulmonary infiltrates present.
  • Presentation due to pure heart failure and no other known risk factors for ALI.
  • Allergy to aspirin or non steroidal anti inflammatory drugs (NSAIDs)
  • Bleeding disorder
  • Suspected active bleeding or judged to be at high risk for bleeding
  • Active peptic ulcer disease (within past 6 months)
  • Severe chronic liver disease
  • Inability to administer the study drug
  • Expected hospital stay < 48 hours
  • Admitted for comfort or hospice care
  • Patient, surrogate or physician not committed to full support. (Exception: a patient will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest)
  • Not anticipated to survive > 48 hours
  • Previously enrolled in this trial
  • Enrolled in a concomitant intervention trial
  • Pregnant or breastfeeding

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboLactose powderThis group received matching lactose powder filled capsules on days 1-7.
AspirinAspirinThis arm received a 325mg loading dose of aspirin on study day one, followed by 81mg of aspirin on days 2-7.
Primary Outcome Measures
NameTimeMethod
Number of Participants Who Developed Acute Respiratory Distress Syndrome (ARDS) Within 7 DaysWithin seven days from hospital presentation

ARDS was defined by Berlin criteria (modified to require invasive mechanical ventilation) within 7 days of hospital admission.

Secondary Outcome Measures
NameTimeMethod
Hospital Mortality28 days
Number of Participants With ARDS or Mortality Within 7 Dayswithin 7 days
Number of Subjects With Mechanical Ventilation at Any Time During Hospitalizationapproximately 7 days
Mean Number of Days Participants Were Ventilator-Free To Day 28baseline, Day 28
Number of Subjects Admitted to Intensive Care Unit (ICU)7 days
Mean Hospital Length of Stayapproximately 7 days

Trial Locations

Locations (16)

Beth Israel Deaconess Medical Center

🇺🇸

Boston, Massachusetts, United States

University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

Bridgeport Hospital

🇺🇸

Bridgeport, Connecticut, United States

Stanford Univeristy

🇺🇸

Stanford, California, United States

Mayo Clinic in Florida

🇺🇸

Jacksonville, Florida, United States

University of Illinois at Chicago

🇺🇸

Chicago, Illinois, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

Brigham and Women's Hospital

🇺🇸

Boston, Massachusetts, United States

University of Louisville Medical Center

🇺🇸

Louisville, Kentucky, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Mayo Clinic in Rochester

🇺🇸

Rochester, Minnesota, United States

Wake Forest University Medical Center

🇺🇸

Winston Salem, North Carolina, United States

Harborview Medical Center

🇺🇸

Seattle, Washington, United States

University of Florida

🇺🇸

Gainsville, Florida, United States

Temple University School of Medicine

🇺🇸

Philadelphia, Pennsylvania, United States

Montefiore Medical Center

🇺🇸

Bronx, New York, United States

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