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

NCT01783821 | Completed Phase 2 Results DMC

• 2 other identifiers: 12-008192UL1RR024150
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 5

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.

Conditions

Acute Respiratory Distress Syndrome (ARDS)

Keywords

Acute respiratory distress syndrome (ARDS)

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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

• Hospital Length of Stay

  Baseline to Day 28

• Intensive Care Unit (ICU) Length of Stay

  Baseline to Day 28

Study Arms (2)

Budesonide and Formoterol

EXPERIMENTAL

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; Drug: Formoterol

Placebo

PLACEBO COMPARATOR

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

Interventions

Budesonide DRUG

Subjects will receive the standard aerosolized dose of budesonide (0.5 mg).

Also known as: Pulmicort

Budesonide and Formoterol

Placebo DRUG

Aerosolized normal saline will be prepared to mimic the intervention arm, with the quantity, appearance and timing of the doses the being the same.

Placebo

Formoterol DRUG

Subjects will receive the standard aerosolized dose of formoterol (20 mcg) .

Also known as: Foradil Aerolizer

Budesonide and Formoterol

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (5)

University of Arizona

Tucson, Arizona, 85721, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

Location

Beth Israel Medical Center

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• 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.

  PMID: 28240689 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome

Interventions

Budesonide; Formoterol Fumarate

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Results Point of Contact

• Title: Dr. Emir Festic
• Organization: Mayo Clinic

Festic.Emir@mayo.edu

904-953-9758

Study Officials

• Emir Festic, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: January 31, 2013
• First Posted: February 5, 2013
• Study Start: July 1, 2013
• Primary Completion: July 1, 2015
• Study Completion: December 1, 2015
• Last Updated: September 5, 2016
• Results First Posted: September 5, 2016

Record last verified: 2016-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)