LIPS-A: Lung Injury Prevention Study With Aspirin
Primary Purpose
Acute Respiratory Distress Syndrome
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Aspirin
Lactose powder
Sponsored by
About this trial
This is an interventional prevention trial for Acute Respiratory Distress Syndrome focused on measuring Acute Respiratory Distress Syndrome, Acute Lung Injury, ARDS, ALI, aspirin, prevention
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
Sites / Locations
- Stanford Univeristy
- Bridgeport Hospital
- University of Florida
- Mayo Clinic in Florida
- University of Illinois at Chicago
- University of Louisville Medical Center
- Massachusetts General Hospital
- Brigham and Women's Hospital
- Beth Israel Deaconess Medical Center
- University of Michigan
- Mayo Clinic in Rochester
- Montefiore Medical Center
- Duke University Medical Center
- Wake Forest University Medical Center
- Temple University School of Medicine
- Harborview Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Aspirin
Placebo
Arm Description
This arm received a 325mg loading dose of aspirin on study day one, followed by 81mg of aspirin on days 2-7.
This group received matching lactose powder filled capsules on days 1-7.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Hospital Mortality
Number of Participants With ARDS or Mortality Within 7 Days
Number of Subjects With Mechanical Ventilation at Any Time During Hospitalization
Mean Number of Days Participants Were Ventilator-Free To Day 28
Number of Subjects Admitted to Intensive Care Unit (ICU)
Mean Hospital Length of Stay
Full Information
NCT ID
NCT01504867
First Posted
January 3, 2012
Last Updated
January 23, 2017
Sponsor
Mayo Clinic
Collaborators
Beth Israel Deaconess Medical Center, Montefiore Medical Center, Vanderbilt University Medical Center, National Heart, Lung, and Blood Institute (NHLBI), National Center for Research Resources (NCRR)
1. Study Identification
Unique Protocol Identification Number
NCT01504867
Brief Title
LIPS-A: Lung Injury Prevention Study With Aspirin
Official Title
LIPS-A: Lung Injury Prevention Study With Aspirin
Study Type
Interventional
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
January 2012 (Actual)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
September 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
Collaborators
Beth Israel Deaconess Medical Center, Montefiore Medical Center, Vanderbilt University Medical Center, National Heart, Lung, and Blood Institute (NHLBI), National Center for Research Resources (NCRR)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Respiratory Distress Syndrome
Keywords
Acute Respiratory Distress Syndrome, Acute Lung Injury, ARDS, ALI, aspirin, prevention
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
400 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Aspirin
Arm Type
Experimental
Arm Description
This arm received a 325mg loading dose of aspirin on study day one, followed by 81mg of aspirin on days 2-7.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
This group received matching lactose powder filled capsules on days 1-7.
Intervention Type
Drug
Intervention Name(s)
Aspirin
Intervention Description
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
Intervention Name(s)
Lactose powder
Intervention Description
Matching lactose powder filled capsules will be administered on days 1-7.
Primary Outcome Measure Information:
Title
Number of Participants Who Developed Acute Respiratory Distress Syndrome (ARDS) Within 7 Days
Description
ARDS was defined by Berlin criteria (modified to require invasive mechanical ventilation) within 7 days of hospital admission.
Time Frame
Within seven days from hospital presentation
Secondary Outcome Measure Information:
Title
Hospital Mortality
Time Frame
28 days
Title
Number of Participants With ARDS or Mortality Within 7 Days
Time Frame
within 7 days
Title
Number of Subjects With Mechanical Ventilation at Any Time During Hospitalization
Time Frame
approximately 7 days
Title
Mean Number of Days Participants Were Ventilator-Free To Day 28
Time Frame
baseline, Day 28
Title
Number of Subjects Admitted to Intensive Care Unit (ICU)
Time Frame
7 days
Title
Mean Hospital Length of Stay
Time Frame
approximately 7 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daryl Kor, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford Univeristy
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Bridgeport Hospital
City
Bridgeport
State/Province
Connecticut
ZIP/Postal Code
06610
Country
United States
Facility Name
University of Florida
City
Gainsville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Mayo Clinic in Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
University of Illinois at Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Louisville Medical Center
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
021114
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Wake Forest University Medical Center
City
Winston Salem
State/Province
North Carolina
ZIP/Postal Code
27517
Country
United States
Facility Name
Temple University School of Medicine
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Facility Name
Harborview Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
27179988
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. Erratum In: JAMA. 2016 Sep 13;316(10):1116.
Results Reference
result
PubMed Identifier
29782179
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.
Results Reference
derived
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LIPS-A: Lung Injury Prevention Study With Aspirin
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