LIPS-A: Lung Injury Prevention Study With Aspirin

NCT ID: NCT01504867

Last Updated: 2017-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2015-09-30

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.

Conditions

Acute Respiratory Distress Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Aspirin

This arm received a 325mg loading dose of aspirin on study day one, followed by 81mg of aspirin on days 2-7.

Group Type: EXPERIMENTAL

Aspirin

Intervention Type: DRUG

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

This group received matching lactose powder filled capsules on days 1-7.

Group Type: PLACEBO_COMPARATOR

Lactose powder

Intervention Type: DRUG

Matching lactose powder filled capsules will be administered on days 1-7.

Interventions

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.

Intervention Type: DRUG

Lactose powder

Matching lactose powder filled capsules will be administered on days 1-7.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: collaborator

Montefiore Medical Center

OTHER

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Daryl J. Kor, M.D.

PI

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daryl Kor, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Temple University School of Medicine

Philadelphia, Pennsylvania, United States

Harborview Medical Center

Seattle, Washington, United States

Stanford Univeristy

Stanford, California, United States

Bridgeport Hospital

Bridgeport, Connecticut, United States

University of Florida

Gainsville, Florida, United States

Mayo Clinic in Florida

Jacksonville, Florida, United States

University of Illinois at Chicago

Chicago, Illinois, United States

University of Louisville Medical Center

Louisville, Kentucky, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Montefiore Medical Center

The Bronx, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Wake Forest University Medical Center

Winston-Salem, North Carolina, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 27179988 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29782179 (View on PubMed)

Other Identifiers

U01HL108712-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

KL2RR024151

Identifier Type: NIH

Identifier Source: secondary_id

View Link

K23HL112855

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UL1TR000433

Identifier Type: NIH

Identifier Source: secondary_id

View Link

10-004856

Identifier Type: -

Identifier Source: org_study_id