The Effect of Nebulized Albuterol on Donor Oxygenation

February 14, 2018 updated by: Lorraine B. Ware, Vanderbilt University Medical Center
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 Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

506

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Oakland, California, United States, 94612
        • California Transplant Donor Network

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Exclusion Criteria

  • Age less than 14 years

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Albuterol
Albuterol sulfate 5 mg dissolved in normal saline administered every 4 hours by nebulization
Drug: Albuterol
5 mg nebulized q4h
Other Names:
  • salbutamol
Placebo Comparator: Saline
Saline administered every 4 hours by nebulization
Drug: Albuterol
5 mg nebulized q4h
Other Names:
  • salbutamol
Drug: Saline
1.0 cc diluted with saline in identical fashion to study drug and administered by nebulizer every 4 hours
Other Names:
  • placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Donor Oxygenation
Time Frame: Change from enrollment to organ procurement (about ~40h after enrollment)
The primary outcome was the change in oxygenation as measured by change in the PaO2/FiO2 ratio from study enrollment to organ procurement
Change from enrollment to organ procurement (about ~40h after enrollment)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Donor Lungs Used for Transplantation
Time Frame: 72 hours
Number of lungs procured and used for transplantation
72 hours
Lung Compliance
Time Frame: baseline and at organ procurement (about ~40h after enrollment)
Static compliance of the respiratory system using plateau pressure (Pplat) measured at end-inspiration and calculated using the equation static compliance = tidal volume/(Pplat - PEEP)
baseline and at organ procurement (about ~40h after enrollment)
Pulmonary Vascular Resistance
Time Frame: 72 hours
72 hours
Chest X-ray Findings
Time Frame: change from enrollment to organ procurement (about ~40h after enrollment)
Chest radiographs were scored using a radiographic score that scored each quadrant for extent of radiographic infiltrates on a scale of 0 to 4, then summed each quadrant for a total score from 0 (no infiltrates) to 16 (extensive infiltrates in all 4 radiographic quadrants).
change from enrollment to organ procurement (about ~40h after enrollment)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University Medical Center

Collaborators

University of California, San Francisco
California Transplant Donor Network

Investigators

  • Principal Investigator: Lorraine B Ware, M.D., Vanderbilt University Medical Center
  • Principal Investigator: Michael A Matthay, M.D., University of California, San Francisco
  • Principal Investigator: Megan Landeck, RN, BSN, APC, California Transplant Donor Network

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2007

Primary Completion (Actual)

May 1, 2011

Study Completion (Actual)

June 1, 2011

Study Registration Dates

First Submitted

March 1, 2006

First Submitted That Met QC Criteria

March 31, 2006

First Posted (Estimate)

April 3, 2006

Study Record Updates

Last Update Posted (Actual)

March 16, 2018

Last Update Submitted That Met QC Criteria

February 14, 2018

Last Verified

February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3U01HL081332-01S1 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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