The Effect of Nebulized Albuterol on Donor Oxygenation

This study has been completed.
Sponsor:
Collaborators:
California Transplant Donor Network
University of California, San Francisco
Information provided by (Responsible Party):
Lorraine B. Ware, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00310401
First received: March 1, 2006
Last updated: August 30, 2013
Last verified: August 2013
  Purpose

The purpose of this study is to test the effectiveness of albuterol versus placebo with the following specific aims: a) Treatment of brain dead organ donors with albuterol will reduce pulmonary edema, improve donor oxygenation, and increase the number of lungs available for transplantation, b) Developing a blood test to predict the development of primary graft dysfunction in lung transplant recipients, and c) treating brain dead organ donors with albuterol will decrease markers of primary graft dysfunction and lead to improved lung transplant recipient outcomes and to higher rates of lungs suitable for transplantation.


Condition Intervention Phase
Brain Death
Organ Donor
Pulmonary Edema
Drug: Albuterol
Drug: Saline
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Nebulized Albuterol on Donor Oxygenation

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Donor Oxygenation [ Time Frame: 72 hours or less ] [ Designated as safety issue: No ]
    The primary outcome was the change in oxygenation as measured by change in the PaO2/FiO2 ratio from study enrollment to organ procurement


Secondary Outcome Measures:
  • Donor Lung Utilization [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Lung Compliance [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Pulmonary Vascular Resistance [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Chest X-ray Findings [ Time Frame: 72 hours ] [ Designated as safety issue: No ]

Enrollment: 506
Study Start Date: April 2007
Study Completion Date: June 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Albuterol Drug: Albuterol
5 mg nebulized q4h
Other Name: salbutamol
Placebo Comparator: Saline Drug: Albuterol
5 mg nebulized q4h
Other Name: salbutamol
Drug: Saline
1.0 cc diluted with saline in identical fashion to study drug and administered by nebulizer every 4 hours

Detailed Description:

The donor lung utilization rate in the United States remains less than 15%, and the demand for donor lungs far exceeds the available supply. The most common reasons for failure to utilize donor lungs are donor hypoxemia and/or pulmonary infiltrates. Since pulmonary edema is a common, reversible cause of hypoxemia and infiltrates in patients with brain injury, strategies to treat pulmonary edema in organ donors should lead to improved donor oxygenation and higher rates of donor lung utilization. Inhaled beta-2 agonists increase the rate of alveolar fluid clearance and reduce pulmonary edema in both animal and human lungs. In addition, our group has recently reported that the majority of human donor lungs that are rejected for transplantation have measurable pulmonary edema and respond to beta-2 agonists with increased rates of alveolar fluid clearance. Based on this compelling scientific evidence, we propose to test the efficacy of an inhaled beta-2 agonist to increase the rate of alveolar fluid clearance and reduce pulmonary edema in brain dead organ donors with the following specific aims:

Specific Aim 1: To test the effect of aerosolized albuterol on donor oxygenation in a multicenter, randomized, double-blinded, placebo-controlled trial in 500 brain dead organ donors managed over a 2 year period by the California Transplant Donor Network (CTDN).

Hypothesis 1a: Treatment of brain dead organ donors with aerosolized albuterol will improve donor oxygenation and increase the donor lung utilization rate compared to treatment with placebo.

Hypothesis 1b: Treatment of brain dead organ donors with aerosolized albuterol will reduce the severity of pulmonary edema in procured lungs compared to treatment with placebo.

Specific Aim 2: To develop and validate a panel of biological markers that can predict and diagnose acute lung injury due to primary graft dysfunction in lung transplant recipients.

Hypothesis 2a: A panel of plasma biological markers measured in brain dead organ donors that includes markers of inflammation, coagulation, endothelial injury and lung epithelial injury will predict the development of primary graft dysfunction in the lung recipient.

Hypothesis 2b: Treatment of brain dead organ donors with inhaled beta-2 agonists will lead to reductions in levels of a panel of biological markers of inflammation, coagulation, endothelial injury, and lung epithelial injury that will be associated with increased donor lung utilization and improved recipient outcomes.

  Eligibility

Ages Eligible for Study:   14 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Brain death
  • Consent for lung donation and donor research
  • Release from coroner or medical examiner

Exclusion Criteria

  • Age less than 14 years
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00310401

Locations
United States, California
California Transplant Donor Network
Oakland, California, United States, 94612
Sponsors and Collaborators
Vanderbilt University
California Transplant Donor Network
University of California, San Francisco
Investigators
Principal Investigator: Lorraine B Ware, M.D. Vanderbilt University
Principal Investigator: Michael A Matthay, M.D. University of California, San Francisco
Principal Investigator: Megan Landeck, RN, BSN, APC California Transplant Donor Network
  More Information

Additional Information:
Publications:

Responsible Party: Lorraine B. Ware, Associate Professor of Medicine, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00310401     History of Changes
Other Study ID Numbers: 3 UO1 HL081332-01S1
Study First Received: March 1, 2006
Results First Received: June 24, 2013
Last Updated: August 30, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Vanderbilt University:
brain death
organ donor
pulmonary edema
albuterol
hypoxia
lung transplantation
infiltrates

Additional relevant MeSH terms:
Brain Death
Death
Edema
Pulmonary Edema
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Coma
Unconsciousness
Consciousness Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Pathologic Processes
Signs and Symptoms
Lung Diseases
Respiratory Tract Diseases
Albuterol
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists

ClinicalTrials.gov processed this record on August 28, 2014