The Effect of Nebulized Albuterol on Donor Oxygenation
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.
|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|
- 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
- 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 ]
|Study Start Date:||April 2007|
|Study Completion Date:||June 2011|
|Primary Completion Date:||May 2011 (Final data collection date for primary outcome measure)|
5 mg nebulized q4h
Other Name: salbutamol
|Placebo Comparator: Saline||
5 mg nebulized q4h
Other Name: salbutamolDrug: Saline
1.0 cc diluted with saline in identical fashion to study drug and administered by nebulizer every 4 hours
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00310401
|United States, California|
|California Transplant Donor Network|
|Oakland, California, United States, 94612|
|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|