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

• ClinicalTrials.gov Identifier: NCT01783821
• Recruitment Status: Completed
• First Posted: February 5, 2013
• Results First Posted: September 5, 2016
• Last Update Posted: September 5, 2016
• Sponsor: Mayo Clinic
• 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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Respiratory Distress Syndrome (ARDS)	Drug: Budesonide; Drug: Placebo; Drug: Formoterol	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 61 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: LIPS-B: Lung Injury Prevention Study With Budesonide and Beta Agonist (Formoterol)
• Study Start Date: July 2013
• Actual Primary Completion Date: July 2015
• Actual Study Completion Date: December 2015

Arms and Interventions

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 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.

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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 Outcome Measures :

1. Number of Subjects Who Needed Mechanical Ventilation [ Time Frame: Hospital discharge, approximately day 28 ]
2. 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.
3. Hospital Length of Stay [ Time Frame: Baseline to Day 28 ]
4. Intensive Care Unit (ICU) Length of Stay [ Time Frame: Baseline to Day 28 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Emir Festic, M.D., Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01783821
• Other Study ID Numbers: 12-008192; UL1RR024150 ( U.S. NIH Grant/Contract )
• First Posted: February 5, 2013
• Results First Posted: September 5, 2016
• Last Update Posted: September 5, 2016
• Last Verified: July 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Emir Festic, Mayo Clinic:

Acute respiratory distress syndrome (ARDS)

Additional relevant MeSH terms:

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