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

Phase 2

Completed

• Conditions: Acute Respiratory Distress Syndrome (ARDS)
• Interventions: Drug: Budesonide; Drug: Placebo; Drug: Formoterol

• Registration Number: NCT01783821
• Lead Sponsor: Mayo Clinic

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.

Study Timeline

• Study First Submitted: 2013-01-31
• Study First Submitted QC: 2013-02-04
• Study First Posted: 2013-02-05
• Study Start: 2013-07
• Primary Completion: 2015-07
• Study Completion: 2015-12
• Results First Submitted: 2016-06-08
• Status Verified: 2016-07
• Results First Submitted QC: 2016-07-22
• Last Update Submitted: 2016-07-22
• Results First Posted: 2016-09-05
• Last Update Posted: 2016-09-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 61

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Budesonide and Formoterol	Budesonide	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	Placebo	Subjects randomized to this arm will receive normal saline, the quantity, appearance and timing of the doses the same as the intervention arm.
Budesonide and Formoterol	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.

Primary Outcome Measures

Name	Time	Method
Change in Oxygen Saturation to Fraction of Inspired Oxygen Concentration (SpO2/FiO2) Ratio	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	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 Outcome Measures

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

Trial Locations

Locations (5)

Mayo Clinic in Florida; 🇺🇸 Jacksonville, Florida, United States

Stanford University; 🇺🇸 Stanford, California, United States

University of Arizona; 🇺🇸 Tucson, Arizona, United States

Beth Israel Medical Center; 🇺🇸 Boston, Massachusetts, United States

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States