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

Overview

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.

Full Title of Study: “LIPS-B: Lung Injury Prevention Study With Budesonide and Beta Agonist (Formoterol)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: July 2015

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.

Interventions

  • Drug: Budesonide
    • Subjects will receive the standard aerosolized dose of budesonide (0.5 mg).
  • 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.
  • Drug: Formoterol
    • Subjects will receive the standard aerosolized dose of formoterol (20 mcg) .

Arms, Groups and Cohorts

  • 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.
  • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Change in Oxygen Saturation to Fraction of Inspired Oxygen Concentration (SpO2/FiO2) Ratio
    • Time Frame: baseline to day 5 after the first treatment
    • 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
    • The data in the table below represent the greatest change from baseline observed for any one participant over all individual post-baseline measurements.

Secondary Measures

  • Number of Subjects Who Needed Mechanical Ventilation
    • Time Frame: Hospital discharge, approximately day 28
  • Number of Subjects Who Developed Acute Respiratory Distress Syndrome (ARDS)
    • Time Frame: Hospital discharge, approximately day 28
    • 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
  • Intensive Care Unit (ICU) Length of Stay
    • Time Frame: Baseline to Day 28

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Mayo Clinic
  • Collaborator
    • Stanford University
  • Provider of Information About this Clinical Study
    • Principal Investigator: Emir Festic, M.D. – Mayo Clinic
  • Overall Official(s)
    • Emir Festic, MD, Principal Investigator, Mayo Clinic

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