The Effect of Nebulized Albuterol on Donor Oxygenation

NCT ID: NCT00310401

Last Updated: 2018-03-16

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

506 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-04-30

Study Completion Date

2011-06-30

Brief Summary

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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

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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.

Conditions

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Brain Death Organ Donor Pulmonary Edema

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Albuterol

Albuterol sulfate 5 mg dissolved in normal saline administered every 4 hours by nebulization

Group Type EXPERIMENTAL

Albuterol

Intervention Type DRUG

5 mg nebulized q4h

Saline

Saline administered every 4 hours by nebulization

Group Type PLACEBO_COMPARATOR

Albuterol

Intervention Type DRUG

5 mg nebulized q4h

Saline

Intervention Type DRUG

1.0 cc diluted with saline in identical fashion to study drug and administered by nebulizer every 4 hours

Interventions

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Albuterol

5 mg nebulized q4h

Intervention Type DRUG

Saline

1.0 cc diluted with saline in identical fashion to study drug and administered by nebulizer every 4 hours

Intervention Type DRUG

Other Intervention Names

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salbutamol placebo

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* Age less than 14 years
Minimum Eligible Age

14 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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California Transplant Donor Network

NETWORK

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Lorraine B. Ware

Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Lorraine B Ware, M.D.

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Michael A Matthay, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Megan Landeck, RN, BSN, APC

Role: PRINCIPAL_INVESTIGATOR

California Transplant Donor Network

Locations

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California Transplant Donor Network

Oakland, California, United States

Site Status

Countries

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United States

References

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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. doi: 10.1111/j.1600-6135.2004.00396.x.

Reference Type BACKGROUND
PMID: 15113353 (View on PubMed)

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. doi: 10.1097/00005373-199511000-00009.

Reference Type BACKGROUND
PMID: 7474001 (View on PubMed)

Simon RP. Neurogenic pulmonary edema. Neurol Clin. 1993 May;11(2):309-23.

Reference Type BACKGROUND
PMID: 8316188 (View on PubMed)

Matthay MA, Folkesson HG, Clerici C. Lung epithelial fluid transport and the resolution of pulmonary edema. Physiol Rev. 2002 Jul;82(3):569-600. doi: 10.1152/physrev.00003.2002.

Reference Type BACKGROUND
PMID: 12087129 (View on PubMed)

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 (1985). 2002 Nov;93(5):1869-74. doi: 10.1152/japplphysiol.00252.2002.

Reference Type BACKGROUND
PMID: 12381777 (View on PubMed)

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. doi: 10.1016/s0140-6736(02)09774-x.

Reference Type BACKGROUND
PMID: 12241936 (View on PubMed)

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. doi: 10.1016/s1053-2498(00)00215-1.

Reference Type BACKGROUND
PMID: 11124490 (View on PubMed)

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. doi: 10.1016/S0022-5223(95)70190-7.

Reference Type BACKGROUND
PMID: 7776671 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14570373 (View on PubMed)

Verghese GM, Ware LB, Matthay BA, Matthay MA. Alveolar epithelial fluid transport and the resolution of clinically severe hydrostatic pulmonary edema. J Appl Physiol (1985). 1999 Oct;87(4):1301-12. doi: 10.1152/jappl.1999.87.4.1301.

Reference Type BACKGROUND
PMID: 10517756 (View on PubMed)

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. doi: 10.1164/ajrccm.163.6.2004035.

Reference Type BACKGROUND
PMID: 11371404 (View on PubMed)

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. doi: 10.1164/ajrccm/142.6_Pt_1.1250.

Reference Type BACKGROUND
PMID: 2252240 (View on PubMed)

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. doi: 10.1164/ajrccm.159.3.9802105.

Reference Type BACKGROUND
PMID: 10051282 (View on PubMed)

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 (1985). 1999 Jan;86(1):139-51. doi: 10.1152/jappl.1999.86.1.139.

Reference Type BACKGROUND
PMID: 9887124 (View on PubMed)

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. doi: 10.1164/ajrccm.150.2.8049807.

Reference Type BACKGROUND
PMID: 8049807 (View on PubMed)

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. doi: 10.1056/NEJMoa013183.

Reference Type BACKGROUND
PMID: 12023995 (View on PubMed)

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. doi: 10.1164/rccm.200508-1302OC. Epub 2005 Oct 27.

Reference Type BACKGROUND
PMID: 16254268 (View on PubMed)

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. doi: 10.1007/s00134-002-1282-x. Epub 2002 May 17.

Reference Type BACKGROUND
PMID: 12107675 (View on PubMed)

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. doi: 10.1164/rccm.200207-670SO.

Reference Type BACKGROUND
PMID: 12588712 (View on PubMed)

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. doi: 10.1097/01.TP.0000066351.87480.9E.

Reference Type BACKGROUND
PMID: 12829889 (View on PubMed)

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. doi: 10.1378/chest.124.4.1232.

Reference Type BACKGROUND
PMID: 14555551 (View on PubMed)

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. doi: 10.1378/chest.121.6.1876.

Reference Type BACKGROUND
PMID: 12065352 (View on PubMed)

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. doi: 10.1016/j.healun.2004.11.049. Epub 2005 Jun 4. No abstract available.

Reference Type BACKGROUND
PMID: 16210116 (View on PubMed)

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. doi: 10.1016/j.healun.2003.09.010. No abstract available.

Reference Type BACKGROUND
PMID: 15477105 (View on PubMed)

Other Identifiers

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3U01HL081332-01S1

Identifier Type: NIH

Identifier Source: org_study_id

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