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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Distress Syndrome (ARDS)
• Intervention / Treatment: Drug: Budesonide; Drug: Formoterol; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85721
      • University of Arizona
  • California
    • Stanford, California, United States, 94305
      • Stanford University
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic in Florida
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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 Names: Pulmicort; Drug: Formoterol; Subjects will receive the standard aerosolized dose of formoterol (20 mcg) .; Other Names: 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Beth Israel Deaconess Medical Center; Stanford University; National Center for Research Resources (NCRR); University of Arizona

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: January 31, 2013
• First Submitted That Met QC Criteria: February 4, 2013
• First Posted (Estimate): February 5, 2013

Study Record Updates

• Last Update Posted (Estimate): September 5, 2016
• Last Update Submitted That Met QC Criteria: July 22, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Acute respiratory distress syndrome (ARDS)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Wounds and Injuries; Infant, Newborn, Diseases; Infant, Premature, Diseases; Thoracic Injuries; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Budesonide; Formoterol Fumarate
• Other Study ID Numbers: 12-008192; UL1RR024150 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO