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LIPS-B: Lung Injury Prevention Study With Budesonide and Beta (LIPS-B)

Primary Purpose

Acute Respiratory Distress Syndrome (ARDS)

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Budesonide
Placebo
Formoterol
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Acute Respiratory Distress Syndrome (ARDS) focused on measuring Acute respiratory distress syndrome (ARDS)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Adult patients (age > 18)
  • Admitted to the hospital through the emergency department (ED)
  • High risk of developing ARDS (Lung Injury Prediction Score (LIPS) greater than or equal to four)

Exclusion Criteria:

  • Inhaled corticosteroid and/or beta agonist treatment on admission or within 7 days prior to admission (history of asthma or COPD necessitating therapy)
  • Chronic pulmonary disease requiring daytime oxygen supplementation therapy
  • Systemic steroid treatment on admission or within 7 days prior to admission equivalent to more than 5 mg of prednisone daily
  • Inability to obtain consent within 12 hours of hospital presentation
  • Acute lung injury prior to randomization
  • Receiving mechanical ventilation before current hospital admission (patient who is ventilator dependent)
  • Presentation believed to be purely due to heart failure without other known risk factors for ARDS
  • Allergy or other contraindication to either budesonide and/or formoterol use
  • Expected hospital stay and/or survival <48 hours or admission 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)
  • Previous enrollment in this trial.
  • Co-enrollment with LIPS-A trial is not allowed.
  • An active enrollment in other concomitant trial will be judged on case by case basis by PIs of both trials.
  • EKG and/or clinical presentation suggestive of acute coronary ischemia
  • New onset cardiac arrhythmia
  • Current atrial fibrillation with ventricular rate of >110/minute
  • Persistent sinus tachycardia of >130/minute despite early goal directed therapy with fluids, pressors, antibiotics and supplemental oxygen
  • Pregnant patients

Sites / Locations

  • University of Arizona
  • Stanford University
  • Mayo Clinic in Florida
  • Beth Israel Medical Center
  • Mayo Clinic in Rochester

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Budesonide and Formoterol

Placebo

Arm Description

Subjects randomized to this arm will receive combined standard aerosolized doses of budesonide (0.5 mg) and formoterol (20 mcg) twice daily, with at least 6 hours between doses, for 5 days for a total of 10 doses or until hospital discharge or death, with the first dose administered as soon as possible following randomization but not later than 4 hours.

Subjects randomized to this arm will receive normal saline, the quantity, appearance and timing of the doses the same as the intervention arm.

Outcomes

Primary Outcome Measures

Change in Oxygen Saturation to Fraction of Inspired Oxygen Concentration (SpO2/FiO2) Ratio
Oxygen saturation (SpO2) was measured by pulse oximetry. FiO2 is the assumed proportion of oxygen concentration participating in gas exchange in the alveoli. All S/F measurements were performed per standard operating protocol using a Venturi mask titrated to obtain an oxygen saturation of 94 ± 2% unless the patient met this goal on room air or clinical status dictated an alternative delivery mode. This outcome measure was analyzed as a longitudinal continuous variable by a mixed effect model. The formula for the calculation of SpO2/FiO2 (or S/F ratio) is %saturation/proportion of FiO2 concentration.
Number of Participants Experiencing Categorical Change in Oxygen Saturation to Fraction of Inspired Oxygen Concentration (SpO2/FiO2) Ratio
The data in the table below represent the greatest change from baseline observed for any one participant over all individual post-baseline measurements.

Secondary Outcome Measures

Number of Subjects Who Needed Mechanical Ventilation
Number of Subjects Who Developed Acute Respiratory Distress Syndrome (ARDS)
ARDS was defined per Berlin definition. Chest radiographs of all ventilated (non-invasive or invasive) patients were reviewed as consistent or not consistent with ARDS by the site investigator. A second adjudication was performed by an alternate principal investigator blinded to subject identification and clinical data. Final diagnosis of ARDS was determined centrally after chest radiograph adjudication was considered together with other relevant clinical data.
Hospital Length of Stay
Intensive Care Unit (ICU) Length of Stay

Full Information

First Posted
January 31, 2013
Last Updated
July 22, 2016
Sponsor
Mayo Clinic
Collaborators
Stanford University, Beth Israel Deaconess Medical Center, University of Arizona, National Center for Research Resources (NCRR)
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1. Study Identification

Unique Protocol Identification Number
NCT01783821
Brief Title
LIPS-B: Lung Injury Prevention Study With Budesonide and Beta
Acronym
LIPS-B
Official Title
LIPS-B: Lung Injury Prevention Study With Budesonide and Beta Agonist (Formoterol)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2016
Overall Recruitment Status
Completed
Study Start Date
July 2013 (undefined)
Primary Completion Date
July 2015 (Actual)
Study Completion Date
December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
Collaborators
Stanford University, Beth Israel Deaconess Medical Center, University of Arizona, National Center for Research Resources (NCRR)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study tested whether inhaled budesonide and formoterol were able to alleviate or prevent pulmonary injury when administered early in hospital course to the patients at risk for developing acute respiratory distress syndrome (ARDS). The FDA has approved many uses for budesonide and formoterol, including asthma and chronic obstructive pulmonary disease (COPD), but the use of these two drugs is experimental for ARDS.
Detailed Description
Subjects were randomized to either placebo or combined standard aerosolized doses of budesonide (0.5 mg) and formoterol (20 mcg) twice daily, with at least 6 hours between doses, for 5 calendar days for a total of 10 doses or until hospital discharge or death. Local hospital pharmacies prepared identical appearing solutions and drug was delivered by respiratory therapists blinded to randomization by using standard jet nebulizers that produce aerosol particle size within the respirable range (<5.5 microns). The first dose was administered within 4 hours after randomization.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Respiratory Distress Syndrome (ARDS)
Keywords
Acute respiratory distress syndrome (ARDS)

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
61 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Budesonide and Formoterol
Arm Type
Experimental
Arm Description
Subjects randomized to this arm will receive combined standard aerosolized doses of budesonide (0.5 mg) and formoterol (20 mcg) twice daily, with at least 6 hours between doses, for 5 days for a total of 10 doses or until hospital discharge or death, with the first dose administered as soon as possible following randomization but not later than 4 hours.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects randomized to this arm will receive normal saline, the quantity, appearance and timing of the doses the same as the intervention arm.
Intervention Type
Drug
Intervention Name(s)
Budesonide
Other Intervention Name(s)
Pulmicort
Intervention Description
Subjects will receive the standard aerosolized dose of budesonide (0.5 mg).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Aerosolized normal saline will be prepared to mimic the intervention arm, with the quantity, appearance and timing of the doses the being the same.
Intervention Type
Drug
Intervention Name(s)
Formoterol
Other Intervention Name(s)
Foradil Aerolizer
Intervention Description
Subjects will receive the standard aerosolized dose of formoterol (20 mcg) .
Primary Outcome Measure Information:
Title
Change in Oxygen Saturation to Fraction of Inspired Oxygen Concentration (SpO2/FiO2) Ratio
Description
Oxygen saturation (SpO2) was measured by pulse oximetry. FiO2 is the assumed proportion of oxygen concentration participating in gas exchange in the alveoli. All S/F measurements were performed per standard operating protocol using a Venturi mask titrated to obtain an oxygen saturation of 94 ± 2% unless the patient met this goal on room air or clinical status dictated an alternative delivery mode. This outcome measure was analyzed as a longitudinal continuous variable by a mixed effect model. The formula for the calculation of SpO2/FiO2 (or S/F ratio) is %saturation/proportion of FiO2 concentration.
Time Frame
baseline to day 5 after the first treatment
Title
Number of Participants Experiencing Categorical Change in Oxygen Saturation to Fraction of Inspired Oxygen Concentration (SpO2/FiO2) Ratio
Description
The data in the table below represent the greatest change from baseline observed for any one participant over all individual post-baseline measurements.
Time Frame
Days 0 - 5
Secondary Outcome Measure Information:
Title
Number of Subjects Who Needed Mechanical Ventilation
Time Frame
Hospital discharge, approximately day 28
Title
Number of Subjects Who Developed Acute Respiratory Distress Syndrome (ARDS)
Description
ARDS was defined per Berlin definition. Chest radiographs of all ventilated (non-invasive or invasive) patients were reviewed as consistent or not consistent with ARDS by the site investigator. A second adjudication was performed by an alternate principal investigator blinded to subject identification and clinical data. Final diagnosis of ARDS was determined centrally after chest radiograph adjudication was considered together with other relevant clinical data.
Time Frame
Hospital discharge, approximately day 28
Title
Hospital Length of Stay
Time Frame
Baseline to Day 28
Title
Intensive Care Unit (ICU) Length of Stay
Time Frame
Baseline to Day 28

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) High risk of developing ARDS (Lung Injury Prediction Score (LIPS) greater than or equal to four) Exclusion Criteria: Inhaled corticosteroid and/or beta agonist treatment on admission or within 7 days prior to admission (history of asthma or COPD necessitating therapy) Chronic pulmonary disease requiring daytime oxygen supplementation therapy Systemic steroid treatment on admission or within 7 days prior to admission equivalent to more than 5 mg of prednisone daily Inability to obtain consent within 12 hours of hospital presentation Acute lung injury prior to randomization Receiving mechanical ventilation before current hospital admission (patient who is ventilator dependent) Presentation believed to be purely due to heart failure without other known risk factors for ARDS Allergy or other contraindication to either budesonide and/or formoterol use Expected hospital stay and/or survival <48 hours or admission 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) Previous enrollment in this trial. Co-enrollment with LIPS-A trial is not allowed. An active enrollment in other concomitant trial will be judged on case by case basis by PIs of both trials. EKG and/or clinical presentation suggestive of acute coronary ischemia New onset cardiac arrhythmia Current atrial fibrillation with ventricular rate of >110/minute Persistent sinus tachycardia of >130/minute despite early goal directed therapy with fluids, pressors, antibiotics and supplemental oxygen Pregnant patients
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emir Festic, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arizona
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85721
Country
United States
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Mayo Clinic in Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Beth Israel Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
28240689
Citation
Festic E, Carr GE, Cartin-Ceba R, Hinds RF, Banner-Goodspeed V, Bansal V, Asuni AT, Talmor D, Rajagopalan G, Frank RD, Gajic O, Matthay MA, Levitt JE. Randomized Clinical Trial of a Combination of an Inhaled Corticosteroid and Beta Agonist in Patients at Risk of Developing the Acute Respiratory Distress Syndrome. Crit Care Med. 2017 May;45(5):798-805. doi: 10.1097/CCM.0000000000002284.
Results Reference
derived

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LIPS-B: Lung Injury Prevention Study With Budesonide and Beta

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