Clinical trial NCT01504867: LIPS-A: Lung Injury Prevention Study With Aspirin
Official title: LIPS-A: Lung Injury Prevention Study With Aspirin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Respiratory Distress Syndrome
Keywords: Acute Respiratory Distress Syndrome
Acute Lung Injury
ARDS
ALI
aspirin
prevention
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Beth Israel Deaconess Medical Center
name: Montefiore Medical Center
name: Vanderbilt University Medical Center
name: National Heart, Lung, and Blood Institute (NHLBI)
name: National Center for Research Resources (NCRR)
First posted: 2012-01-06
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Number of Participants Who Developed Acute Respiratory Distress Syndrome (ARDS) Within 7 Days
timeFrame: Within seven days from hospital presentation
Secondary outcomes:
measure: Hospital Mortality
timeFrame: 28 days
measure: Number of Participants With ARDS or Mortality Within 7 Days
timeFrame: within 7 days
measure: Number of Subjects With Mechanical Ventilation at Any Time During Hospitalization
timeFrame: approximately 7 days
measure: Mean Number of Days Participants Were Ventilator-Free To Day 28
timeFrame: baseline, Day 28
measure: Number of Subjects Admitted to Intensive Care Unit (ICU)
timeFrame: 7 days
measure: Mean Hospital Length of Stay
timeFrame: approximately 7 days
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Univeristy
state: California
city: Bridgeport
country: United States
facility: Bridgeport Hospital
state: Connecticut
city: Gainsville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Louisville
country: United States
facility: University of Louisville Medical Center
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston Salem
country: United States
facility: Wake Forest University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: Temple University School of Medicine
state: Pennsylvania
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
Study officials:
affiliation: Mayo Clinic
name: Daryl Kor, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.