LIPS-A: Lung Injury Prevention Study With Aspirin

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.

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: Aspirin; Drug: Lactose powder

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.

• Study Type: Interventional
• Enrollment (Actual): 400
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford Univeristy
  • Connecticut
    • Bridgeport, Connecticut, United States, 06610
      • Bridgeport Hospital
  • Florida
    • Gainsville, Florida, United States, 32610
      • University of Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic in Florida
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 021114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston Salem, North Carolina, United States, 27517
      • Wake Forest University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University School of Medicine
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aspirin; This arm received a 325mg loading dose of aspirin on study day one, followed by 81mg of aspirin on days 2-7.	Drug: Aspirin; 325mg loading dose once on study day 1, followed by 81mg dose once daily on study days 2-7. Administered by mouth or down nasal gastric tube.
Placebo Comparator: Placebo; This group received matching lactose powder filled capsules on days 1-7.	Drug: Lactose powder; Matching lactose powder filled capsules will be administered on days 1-7.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Developed Acute Respiratory Distress Syndrome (ARDS) Within 7 Days	ARDS was defined by Berlin criteria (modified to require invasive mechanical ventilation) within 7 days of hospital admission.	Within seven days from hospital presentation

Secondary Outcome Measures

Outcome Measure	Time Frame
Hospital Mortality	28 days
Number of Participants With ARDS or Mortality Within 7 Days	within 7 days
Number of Subjects With Mechanical Ventilation at Any Time During Hospitalization	approximately 7 days
Mean Number of Days Participants Were Ventilator-Free To Day 28	baseline, Day 28
Number of Subjects Admitted to Intensive Care Unit (ICU)	7 days
Mean Hospital Length of Stay	approximately 7 days

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Beth Israel Deaconess Medical Center; Montefiore Medical Center; Vanderbilt University Medical Center; National Center for Research Resources (NCRR)
• Investigators: Principal Investigator: Daryl Kor, MD, Mayo Clinic

Publications and helpful links

General Publications

• Kor DJ, Carter RE, Park PK, Festic E, Banner-Goodspeed VM, Hinds R, Talmor D, Gajic O, Ware LB, Gong MN; US Critical Illness and Injury Trials Group: Lung Injury Prevention with Aspirin Study Group (USCIITG: LIPS-A). Effect of Aspirin on Development of ARDS in At-Risk Patients Presenting to the Emergency Department: The LIPS-A Randomized Clinical Trial. JAMA. 2016 Jun 14;315(22):2406-14. doi: 10.1001/jama.2016.6330. Erratum In: JAMA. 2016 Sep 13;316(10):1116.
• Abdulnour RE, Gunderson T, Barkas I, Timmons JY, Barnig C, Gong M, Kor DJ, Gajic O, Talmor D, Carter RE, Levy BD. Early Intravascular Events Are Associated with Development of Acute Respiratory Distress Syndrome. A Substudy of the LIPS-A Clinical Trial. Am J Respir Crit Care Med. 2018 Jun 15;197(12):1575-1585. doi: 10.1164/rccm.201712-2530OC.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2012
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: January 3, 2012
• First Submitted That Met QC Criteria: January 5, 2012
• First Posted (Estimate): January 6, 2012

Study Record Updates

• Last Update Posted (Actual): March 6, 2017
• Last Update Submitted That Met QC Criteria: January 23, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: prevention; ARDS; Acute Respiratory Distress Syndrome; aspirin; Acute Lung Injury; ALI
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Wounds and Injuries; Infant, Newborn, Diseases; Infant, Premature, Diseases; Thoracic Injuries; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: 10-004856; U01HL108712-01 (U.S. NIH Grant/Contract); KL2RR024151 (U.S. NIH Grant/Contract); K23HL112855 (U.S. NIH Grant/Contract); UL1TR000433 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED