LIPS-A: Lung Injury Prevention Study With Aspirin

Study Overview
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Brief Summary
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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
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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.

Official Title
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LIPS-A: Lung Injury Prevention Study With Aspirin

Conditions
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Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: Aspirin
* Drug: Lactose powder


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aspirin<br>This arm received a 325mg loading dose of aspirin on study day one, followed by 81mg of aspirin on days 2-7. | Drug: Aspirin<br>* 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.<br>|
| Placebo Comparator: Placebo<br>This group received matching lactose powder filled capsules on days 1-7. | Drug: Lactose powder<br>* Matching lactose powder filled capsules will be administered on days 1-7.<br>|

What is the study measuring?
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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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Respiratory Distress Syndrome, Acute Lung Injury, ARDS, ALI, aspirin, prevention