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

Study Overview
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Brief Summary
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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
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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.

Official Title
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LIPS-B: Lung Injury Prevention Study With Budesonide and Beta Agonist (Formoterol)

Conditions
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Acute Respiratory Distress Syndrome (ARDS)

Intervention / Treatment
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* Drug: Budesonide
* Drug: Placebo
* Drug: Formoterol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Budesonide and Formoterol<br>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<br>* Subjects will receive the standard aerosolized dose of budesonide (0.5 mg).<br>* Other names: Pulmicort;Drug: Formoterol<br>* Subjects will receive the standard aerosolized dose of formoterol (20 mcg) .<br>* Other names: Foradil Aerolizer;|
| Placebo Comparator: Placebo<br>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<br>* Aerosolized normal saline will be prepared to mimic the intervention arm, with the quantity, appearance and timing of the doses the being the same.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | baseline to day 5 after the first treatment | 
| 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. | Days 0 - 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Who Needed Mechanical Ventilation |  | Hospital discharge, approximately day 28 | 
| 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 discharge, approximately day 28 | 
| Hospital Length of Stay |  | Baseline to Day 28 | 
| Intensive Care Unit (ICU) Length of Stay |  | Baseline to Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute respiratory distress syndrome (ARDS)