Drug Study of Albuterol to Treat Acute Lung Injury

NCT ID: NCT00434993

Last Updated: 2017-02-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 282 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31
• Study Completion Date: 2008-11-30

Brief Summary

Acute Respiratory Distress Syndrome (ARDS) and a lesser condition that occurs prior to ARDS, Acute Lung Injury (ALI), are medical conditions that occur when there is severe inflammation and increased fluids (edema) in both lungs, making it hard for the lungs to function properly. Patients with these conditions require treatment that includes the use of a breathing machine (ventilator). The purpose of this study is to find out whether giving albuterol (a drug commonly used in asthmatics) or not giving albuterol to patients with ALI or ARDS makes a difference in how long it takes for a patient to be able to breath without the ventilator.

Detailed Description

Aerosolized beta-2 agonist therapy is anticipated to diminish the formation of lung edema, enhance clearance of lung edema and decrease pulmonary inflammation in patients with acute lung injury. Because beta-2 agonists have been shown to reduce permeability induced lung injury, it is anticipated that the severity of lung injury will be reduced by aerosolized beta-2 agonist therapy. The therapy may work by enhancing resolution of pulmonary edema by upregulating alveolar epithelial fluid transport mechanisms that will in turn enhance the clearance of alveolar edema. A reduction in the severity of lung injury and the quantity of alveolar edema should result in earlier extubation and more ventilator free days, improved pulmonary oxygen uptake, and improved lung compliance.

Study design: phase II/III prospective, randomized double-blind, placebo controlled trial.

• In Phase II, patients will be treated with aerosolized albuterol 5.0 mg vs. normal saline (n=40-50)administered every 4 hours for 10 days following randomization or until 24 hours following extubation, whichever occurs first. The protocol stipulates that the 5.0 mg dose will be reduced to 2.5 mg if patients exceed defined heart rate limits.
• In Phase III, the 5.0 mg dose will be used unless there is evidence that this dose has an unacceptable safety profile or dose reductions for tachycardia occur in a large fraction of patients. In that case, a lower dose of 2.5 mg will be used.
• Patients will be followed for 90 days or until discharge from the hospital to home with unassisted breathing whichever occurs first.

Conditions

Respiratory Distress Syndrome, Adult

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Albuterol Sulfate

Group Type: ACTIVE_COMPARATOR

Albuterol Sulfate

Intervention Type: DRUG

Albuterol sulfate, USP, solution for inhalation will be diluted as follows:

• The full dose of 5.0 mg will be diluted into 2.0 ml of sterile normal saline solution.
• The reduced dose of 2.5 mg will be diluted into 2.5 ml of sterile normal saline solution.

A high-efficiency small volume jet nebulizer (SVN) powered at a flow of 8 liters/minute from a 50 psi wall oxygen flow meter will be used for continuous nebulization. The study drug will be given every 4 hours (plus or minus one hour) for ten days following randomization or until 24 hours after extubation, whichever occurs first.

Mini-Bronchoalveolar Lavage (BAL)

Intervention Type: PROCEDURE

The mini-BAL procedure involves blind specimen sampling from distal airspaces. Specimens are obtained with the Combicath (Plastimed) catheter. The procedure will be done on study days 0 and 3

Placebo

Group Type: PLACEBO_COMPARATOR

Mini-Bronchoalveolar Lavage (BAL)

Intervention Type: PROCEDURE

The mini-BAL procedure involves blind specimen sampling from distal airspaces. Specimens are obtained with the Combicath (Plastimed) catheter. The procedure will be done on study days 0 and 3

Placebo

Intervention Type: DRUG

Placebo aerosol will consist of 3.0 ml of identical appearing sterile 0.9 % sodium chloride without preservative.

A high-efficiency small volume jet nebulizer (SVN) powered at a flow of 8 liters/minute from a 50 psi wall oxygen flow meter will be used for continuous nebulization (e.g.: throughout the inspiratory and expiratory cycle).

The study drug will be given every 4 hours (plus or minus one hour) for ten days following randomization or until 24 hours after extubation, whichever occurs first.

Interventions

Albuterol Sulfate

Albuterol sulfate, USP, solution for inhalation will be diluted as follows:

• The full dose of 5.0 mg will be diluted into 2.0 ml of sterile normal saline solution.
• The reduced dose of 2.5 mg will be diluted into 2.5 ml of sterile normal saline solution.

A high-efficiency small volume jet nebulizer (SVN) powered at a flow of 8 liters/minute from a 50 psi wall oxygen flow meter will be used for continuous nebulization. The study drug will be given every 4 hours (plus or minus one hour) for ten days following randomization or until 24 hours after extubation, whichever occurs first.

Intervention Type: DRUG

Mini-Bronchoalveolar Lavage (BAL)

The mini-BAL procedure involves blind specimen sampling from distal airspaces. Specimens are obtained with the Combicath (Plastimed) catheter. The procedure will be done on study days 0 and 3

Intervention Type: PROCEDURE

Placebo

Placebo aerosol will consist of 3.0 ml of identical appearing sterile 0.9 % sodium chloride without preservative.

A high-efficiency small volume jet nebulizer (SVN) powered at a flow of 8 liters/minute from a 50 psi wall oxygen flow meter will be used for continuous nebulization (e.g.: throughout the inspiratory and expiratory cycle).

The study drug will be given every 4 hours (plus or minus one hour) for ten days following randomization or until 24 hours after extubation, whichever occurs first.

Intervention Type: DRUG

Other Intervention Names

0.9% sodium chloride; Combicath; 0.9% sodium chloride

Eligibility Criteria

Inclusion Criteria

• Must meet the following three criteria within a 24-hour period:

1. Acute onset of PaO2/FiO2 less than or equal to 300 (adjustments made for altitude where appropriate)

2. Bilateral infiltrates consistent with pulmonary edema on frontal chest radiograph

3. Requirement for positive pressure ventilation via endotracheal tube

• No clinical evidence of left-sided cardiac failure to account for bilateral pulmonary infiltrates

• Neuromuscular disease that impairs ability to ventilate without assistance, (e.g., cervical spinal cord injury at level C5 or higher spinal cord injury amyotrophic lateral sclerosis, Guillain-Barré syndrome or myasthenia gravis)
• Pregnant or breast-feeding
• Severe chronic respiratory disease (i.e., chronic hypercapnia [PaCO2 greater than 45 mmHg], chronic hypoxemia [PaO2 less than 55 mmHg on FiO2 = 0.21], hospitalization within the last 6 months for respiratory failure [PaCO2 greater than 50 mm Hg and/or PaO2 less than 55 mmHg on 0.21 FiO2], secondary polycythemia, severe pulmonary hypertension [mean PAP (pulmonary artery pressure) greater than 40 mmHg], or ventilator dependency)
• Burns over greater than 40% of total body surface area
• Cancer or other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%
• Allogeneic bone marrow transplant within the 5 years prior to study entry
• Participant, surrogate, or physician is not committed to full support (Exception: a participant will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest)
• Severe chronic liver disease (Child-Pugh score of 11-15)
• Diffuse alveolar hemorrhage from vasculitis
• Morbid obesity (greater than 1kg/cm body weight.)
• Unwillingness or inability to utilize the ARDS network 6 ml / kg Predicted Body Weight (PBW) ventilation protocol
• Moribund participant and is not expected to survive 24 hours
• No intent to obtain central venous access for monitoring intravascular pressures
• Contraindication to aerosolized albuterol (see Appendix A.8 of the protocol for more information)
• Daily use (prior to study hospitalization) of inhaled beta agonist, corticosteroid, or oral leukotriene modifier
• Unwillingness of primary physician to discontinue inpatient beta agonist use
• Acute myocardial infarction or acute coronary syndrome within 30 days of study entry
• Severe congestive heart failure (see Appendix A5 of the protocol for more information)
• Participation in other experimental medication trial within 30 days of study entry with the exception of the ARDSNet pharmaconutrient nutrition trial (OMEGA)
• Heart rate greater than 85% of maximal predicted heart rate (MHR85) as calculated by MHR85 = 85% x (220-age)
• Currently receiving high frequency ventilation

• Minimum Eligible Age: 13 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael A. Matthay, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Roy Brower, MD

Role: STUDY_CHAIR

Johns Hopkins University

Locations

University of San Francisco-Fresno Medical Center

Fresno, California, United States

University of California, Davis Medical Center

Sacramento, California, United States

UCSF-Moffitt Hospital

San Francisco, California, United States

UCSF-San Francisco General Hospital

San Francisco, California, United States

Centura St. Anthony Central Hospital

Denver, Colorado, United States

Denver Health Medical Center

Denver, Colorado, United States

Rose Medical Center

Denver, Colorado, United States

University of Colorado Health Sciences Center

Denver, Colorado, United States

Washington Hospital Center

Washington D.C., District of Columbia, United States

Baton Rouge General Hospital-Blue Bonnet

Baton Rouge, Louisiana, United States

Baton Rouge General Hospital-Midcity

Baton Rouge, Louisiana, United States

Earl K. Long Medical Center

Baton Rouge, Louisiana, United States

Our Lady of the Lake Regional Medical Center

Baton Rouge, Louisiana, United States

Medical Center of Louisiana

New Orleans, Louisiana, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Tulane University Health Sciences Center

New Orleans, Louisiana, United States

Baltimore VA Medical Center

Baltimore, Maryland, United States

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

University of Maryland Shock Trauma Center

Baltimore, Maryland, United States

Baystate Medical Center

Springfield, Massachusetts, United States

Rochester Methodist Hospital

Rochester, Minnesota, United States

St. Mary's Hospital, Mayo Clinic

Rochester, Minnesota, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Durham Regional Medical Center

Durham, North Carolina, United States

Moses Cone Health System

Greensboro, North Carolina, United States

Wesley Long Community Hospital

Greensboro, North Carolina, United States

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

MetroHealth Medical Center

Cleveland, Ohio, United States

University Hospitals of Cleveland

Cleveland, Ohio, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Baylor College of Medicine

Houston, Texas, United States

McKay-Dee Hospital

Ogden, Utah, United States

Utah Valley Regional Medical Center

Provo, Utah, United States

LDS Hospital

Salt Lake City, Utah, United States

University of Virginia Medical Center

Charlottesville, Virginia, United States

Harborview Medical Center

Seattle, Washington, United States

University of Washington

Seattle, Washington, United States

Countries

United States

References

Brown SM, Wilson E, Presson AP, Zhang C, Dinglas VD, Greene T, Hopkins RO, Needham DM; with the National Institutes of Health NHLBI ARDS Network. Predictors of 6-month health utility outcomes in survivors of acute respiratory distress syndrome. Thorax. 2017 Apr;72(4):311-317. doi: 10.1136/thoraxjnl-2016-208560. Epub 2016 Jul 20.

Reference Type: DERIVED

PMID: 27440140 (View on PubMed)

Ambrus DB, Benjamin EJ, Bajwa EK, Hibbert KA, Walkey AJ. Risk factors and outcomes associated with new-onset atrial fibrillation during acute respiratory distress syndrome. J Crit Care. 2015 Oct;30(5):994-7. doi: 10.1016/j.jcrc.2015.06.003. Epub 2015 Jun 16.

Reference Type: DERIVED

PMID: 26138630 (View on PubMed)

National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network; Matthay MA, Brower RG, Carson S, Douglas IS, Eisner M, Hite D, Holets S, Kallet RH, Liu KD, MacIntyre N, Moss M, Schoenfeld D, Steingrub J, Thompson BT. Randomized, placebo-controlled clinical trial of an aerosolized beta(2)-agonist for treatment of acute lung injury. Am J Respir Crit Care Med. 2011 Sep 1;184(5):561-8. doi: 10.1164/rccm.201012-2090OC.

Reference Type: DERIVED

PMID: 21562125 (View on PubMed)

Study Documents

Document Type: Individual Participant Data Set

NHLBI provides controlled access to IPD through BioLINCC. Access requires registration, evidence of local IRB approval or certification of exemption from IRB review, and completion of a data use agreement.

View Document

Document Type: Study Protocol

View Document

Document Type: Study Forms

View Document

Related Links

http://www.ardsnet.org

NHLBI Acute Respiratory Distress Syndrome Network Website

Other Identifiers

N01HR056179

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HHSN268200536179C

Identifier Type: -

Identifier Source: secondary_id

474

Identifier Type: -

Identifier Source: org_study_id