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The Effect of Nebulized Albuterol on Donor Oxygenation
This study is currently recruiting participants.
Verified by Vanderbilt University, December 2008
First Received: March 1, 2006   Last Updated: December 18, 2008   History of Changes
Sponsors and Collaborators: Vanderbilt University
California Transplant Donor Network
University of California, San Francisco
Information provided by: Vanderbilt University
ClinicalTrials.gov Identifier: NCT00310401
  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
Phase II

MedlinePlus related topics: Edema Lung Transplantation
Drug Information available for: Albuterol Levalbuterol hydrochloride Albuterol sulfate Levalbuterol tartrate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title: The Effect of Nebulized Albuterol on Donor Oxygenation

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • Donor oxygenation [ Time Frame: 72 hours ] [ Designated as safety issue: No ]

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 ]

Estimated Enrollment: 500
Study Start Date: April 2007
Estimated Study Completion Date: March 2011
Estimated Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Albuterol
    5 mg nebulized q4h
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
  • Release from coroner or medical examiner
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00310401

Contacts
Contact: Lorraine B Ware, M.D. 615-322-7828 lorraine.ware@vanderbilt.edu
Contact: Michael A Matthay, M.D. 415-353-1210 michael.matthay@ucsf.edu

Locations
United States, California
California Transplant Donor Network Recruiting
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:
Ojo AO, Heinrichs D, Emond JC, McGowan JJ, Guidinger MK, Delmonico FL, Metzger RA. Organ donation and utilization in the USA. Am J Transplant. 2004;4 Suppl 9:27-37.
Rogers FB, Shackford SR, Trevisani GT, Davis JW, Mackersie RC, Hoyt DB. Neurogenic pulmonary edema in fatal and nonfatal head injuries. J Trauma. 1995 Nov;39(5):860-6; discussion 866-8.
Simon RP. Neurogenic pulmonary edema. Neurol Clin. 1993 May;11(2):309-23. Review.
Matthay MA, Folkesson HG, Clerici C. Lung epithelial fluid transport and the resolution of pulmonary edema. Physiol Rev. 2002 Jul;82(3):569-600. Review.
Ware LB, Fang X, Wang Y, Sakuma T, Hall TS, Matthay MA. Selected contribution: mechanisms that may stimulate the resolution of alveolar edema in the transplanted human lung. J Appl Physiol. 2002 Nov;93(5):1869-74.
Ware LB, Wang Y, Fang X, Warnock M, Sakuma T, Hall TS, Matthay M. Assessment of lungs rejected for transplantation and implications for donor selection. Lancet. 2002 Aug 24;360(9333):619-20.
Bhorade SM, Vigneswaran W, McCabe MA, Garrity ER. Liberalization of donor criteria may expand the donor pool without adverse consequence in lung transplantation. J Heart Lung Transplant. 2000 Dec;19(12):1199-204.
Sundaresan S, Semenkovich J, Ochoa L, Richardson G, Trulock EP, Cooper JD, Patterson GA. Successful outcome of lung transplantation is not compromised by the use of marginal donor lungs. J Thorac Cardiovasc Surg. 1995 Jun;109(6):1075-9; discussion 1079-80.
Whiting D, Banerji A, Ross D, Levine M, Shpiner R, Lackey S, Ardehali A. Liberalization of donor criteria in lung transplantation. Am Surg. 2003 Oct;69(10):909-12.
Verghese GM, Ware LB, Matthay BA, Matthay MA. Alveolar epithelial fluid transport and the resolution of clinically severe hydrostatic pulmonary edema. J Appl Physiol. 1999 Oct;87(4):1301-12.
Ware LB, Matthay MA. Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med. 2001 May;163(6):1376-83.
Matthay MA, Wiener-Kronish JP. Intact epithelial barrier function is critical for the resolution of alveolar edema in humans. Am Rev Respir Dis. 1990 Dec;142(6 Pt 1):1250-7.
Ware LB, Golden JA, Finkbeiner WE, Matthay MA. Alveolar epithelial fluid transport capacity in reperfusion lung injury after lung transplantation. Am J Respir Crit Care Med. 1999 Mar;159(3):980-8.
Campbell AR, Folkesson HG, Berthiaume Y, Gutkowska J, Suzuki S, Matthay MA. Alveolar epithelial fluid clearance persists in the presence of moderate left atrial hypertension in sheep. J Appl Physiol. 1999 Jan;86(1):139-51.
Sakuma T, Okaniwa G, Nakada T, Nishimura T, Fujimura S, Matthay MA. Alveolar fluid clearance in the resected human lung. Am J Respir Crit Care Med. 1994 Aug;150(2):305-10.
Sartori C, Allemann Y, Duplain H, Lepori M, Egli M, Lipp E, Hutter D, Turini P, Hugli O, Cook S, Nicod P, Scherrer U. Salmeterol for the prevention of high-altitude pulmonary edema. N Engl J Med. 2002 May 23;346(21):1631-6.
Perkins GD, McAuley DF, Thickett DR, Gao F. The beta-agonist lung injury trial (BALTI): a randomized placebo-controlled clinical trial. Am J Respir Crit Care Med. 2006 Feb 1;173(3):281-7. Epub 2005 Oct 27.
Atabai K, Ware LB, Snider ME, Koch P, Daniel B, Nuckton TJ, Matthay MA. Aerosolized beta(2)-adrenergic agonists achieve therapeutic levels in the pulmonary edema fluid of ventilated patients with acute respiratory failure. Intensive Care Med. 2002 Jun;28(6):705-11. Epub 2002 May 17.
de Perrot M, Liu M, Waddell TK, Keshavjee S. Ischemia-reperfusion-induced lung injury. Am J Respir Crit Care Med. 2003 Feb 15;167(4):490-511. Review.
Avlonitis VS, Fisher AJ, Kirby JA, Dark JH. Pulmonary transplantation: the role of brain death in donor lung injury. Transplantation. 2003 Jun 27;75(12):1928-33. Review.
Christie JD, Kotloff RM, Pochettino A, Arcasoy SM, Rosengard BR, Landis JR, Kimmel SE. Clinical risk factors for primary graft failure following lung transplantation. Chest. 2003 Oct;124(4):1232-41.
Thabut G, Vinatier I, Stern JB, Leseche G, Loirat P, Fournier M, Mal H. Primary graft failure following lung transplantation: predictive factors of mortality. Chest. 2002 Jun;121(6):1876-82.
Christie JD, Carby M, Bag R, Corris P, Hertz M, Weill D; ISHLT Working Group on Primary Lung Graft Dysfunction. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part II: definition. A consensus statement of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2005 Oct;24(10):1454-9. Epub 2005 Jun 4. No abstract available.
de Perrot M, Snell GI, Babcock WD, Meyers BF, Patterson G, Hodges TN, Keshavjee S. Strategies to optimize the use of currently available lung donors. J Heart Lung Transplant. 2004 Oct;23(10):1127-34. No abstract available.

Responsible Party: Vanderbilt University ( Lorraine B Ware, M.D. )
Study ID Numbers: 3 UO1 HL081332-01S1
Study First Received: March 1, 2006
Last Updated: December 18, 2008
ClinicalTrials.gov Identifier: NCT00310401     History of Changes
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

Study placed in the following topic categories:
Neurotransmitter Agents
Death
Unconsciousness
Adrenergic beta-Agonists
Adrenergic Agents
Brain Death
Albuterol
Consciousness Disorders
Anti-Asthmatic Agents
Edema
Central Nervous System Diseases
Brain Diseases
Adrenergic Agonists
Coma
Signs and Symptoms
Pulmonary Edema
Respiratory Tract Diseases
Lung Diseases
Neurologic Manifestations
Peripheral Nervous System Agents
Bronchodilator Agents
Neurobehavioral Manifestations

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

ClinicalTrials.gov processed this record on May 07, 2009