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

This study has been completed.
Sponsor:
Collaborators:
Stanford University
Beth Israel Deaconess Medical Center
University of Arizona
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
Emir Festic, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01783821
First received: January 31, 2013
Last updated: July 22, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Acute Respiratory Distress Syndrome (ARDS)
Drug: Budesonide
Drug: Placebo
Drug: Formoterol
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: LIPS-B: Lung Injury Prevention Study With Budesonide and Beta Agonist (Formoterol)

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Change in Oxygen Saturation to Fraction of Inspired Oxygen Concentration (SpO2/FiO2) Ratio [ Time Frame: baseline to day 5 after the first treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 0 - 5 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Hospital discharge, approximately day 28 ] [ Designated as safety issue: No ]
  • Number of Subjects Who Developed Acute Respiratory Distress Syndrome (ARDS) [ Time Frame: Hospital discharge, approximately day 28 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline to Day 28 ] [ Designated as safety issue: No ]
  • Intensive Care Unit (ICU) Length of Stay [ Time Frame: Baseline to Day 28 ] [ Designated as safety issue: No ]

Enrollment: 61
Study Start Date: July 2013
Study Completion Date: December 2015
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Budesonide and Formoterol
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.
Drug: Budesonide
Subjects will receive the standard aerosolized dose of budesonide (0.5 mg).
Other Name: Pulmicort
Drug: Formoterol
Subjects will receive the standard aerosolized dose of formoterol (20 mcg) .
Other Name: Foradil Aerolizer
Placebo Comparator: Placebo
Subjects randomized to this arm will receive normal saline, the quantity, appearance and timing of the doses the same as the intervention arm.
Drug: Placebo
Aerosolized normal saline will be prepared to mimic the intervention arm, with the quantity, appearance and timing of the doses the being the same.

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01783821

Locations
United States, Arizona
University of Arizona
Tucson, Arizona, United States, 85721
United States, California
Stanford University
Stanford, California, United States, 94305
United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224
United States, Massachusetts
Beth Israel Medical Center
Boston, Massachusetts, United States, 02215
United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Stanford University
Beth Israel Deaconess Medical Center
University of Arizona
National Center for Research Resources (NCRR)
Investigators
Principal Investigator: Emir Festic, MD Mayo Clinic
  More Information

Responsible Party: Emir Festic, M.D., Mayo Clinic
ClinicalTrials.gov Identifier: NCT01783821     History of Changes
Other Study ID Numbers: 12-008192  UL1RR024150 
Study First Received: January 31, 2013
Results First Received: June 8, 2016
Last Updated: July 22, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Mayo Clinic:
Acute respiratory distress syndrome (ARDS)

Additional relevant MeSH terms:
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Lung Injury
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Thoracic Injuries
Wounds and Injuries
Formoterol Fumarate
Budesonide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on December 09, 2016