Clinical trial NCT00310401: The Effect of Nebulized Albuterol on Donor Oxygenation
Official title: The Effect of Nebulized Albuterol on Donor Oxygenation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain Death
Organ Donor
Pulmonary Edema
Keywords: brain death
organ donor
pulmonary edema
albuterol
hypoxia
lung transplantation
infiltrates
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: California Transplant Donor Network
name: University of California, San Francisco
First posted: 2006-04-03
Enrollment: 506
Sex: ALL
Minimum age (years): 14
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Donor Oxygenation
timeFrame: Change from enrollment to organ procurement (about ~40h after enrollment)
Secondary outcomes:
measure: Number of Donor Lungs Used for Transplantation
timeFrame: 72 hours
measure: Lung Compliance
timeFrame: baseline and at organ procurement (about ~40h after enrollment)
measure: Pulmonary Vascular Resistance
timeFrame: 72 hours
measure: Chest X-ray Findings
timeFrame: change from enrollment to organ procurement (about ~40h after enrollment)
Other outcomes:
Locations:
city: Oakland
country: United States
facility: California Transplant Donor Network
state: California
Study officials:
affiliation: Vanderbilt University Medical Center
name: Lorraine B Ware, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Michael A Matthay, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: California Transplant Donor Network
name: Megan Landeck, RN, BSN, APC
role: PRINCIPAL_INVESTIGATOR
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