Clinical trial NCT02376387: Evidence Based Evaluation and Acceptance of Donor Hearts for Transplantation
Official title: Evidence Based Evaluation and Acceptance of Donor Hearts for Transplantation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Transplantation
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Oregon Health and Science University
name: Kaiser Permanente
name: California Transplant Donor Network
name: Donor Network of Arizona
name: Gift of Life
name: Gift of Hope
name: LifeLink
name: New England Organ Bank
name: Life Gift Organ Donation
name: National Institutes of Health (NIH)
First posted: 2015-03-03
Enrollment: 4333
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Brain dead donors for heart transplant

Brief summary: The proposed research will provide evidence-based strategies for the evaluation and acceptance of donor hearts for transplantation. This is relevant to public health because judicious expansion of donor hearts used for transplantation will make this life-saving procedure available to a larger number of patients living with end-stage heart disease.

Detailed description: The demand for donor hearts for transplantation far outstrips the supply; however, only one in three available cardiac grafts are used for transplantation. There are many reasons for graft non-use, but previous studies have failed to demonstrate consistent associations between donor characteristics, donor cardiac function, and adverse recipient outcomes. Thus, there is a critical need to standardize how cardiac allografts are evaluated and accepted for transplantation. The investigators long-term goal is to safely expand the use of available cardiac allografts without adversely affecting transplant recipient outcomes. The investigators propose to carefully characterize the current population of cardiac organ donors, particularly with regards to allograft function; to examine how decisions are made regarding graft acceptance for transplantation; and to systematically evaluate associations between donor characteristics and recipient outcomes. The investigators central hypothesis is that acceptable allografts for heart transplantation are being unnecessarily discarded, and the establishment of an evidence-based process for cardiac donor evaluation and acceptance will increase graft utilization rates while maintaining excellent clinical outcomes. In response to this need, the investigators propose a collaborative study with seven organ procurement organizations representing geographically diverse regions of the United States, to address the following specific aims: (1) To identify clinical correlates of graft function in potential donors being evaluated for heart transplantation. An existing online donor research database will be expanded for standardized collection of data on detailed donor characteristics, especially as pertains to cardiac allograft function. The investigators will perform expert core review of donor echocardiograms, including serial echocardiograms in donors with cardiac allograft dysfunction. Serial electrocardiograms and cardiac biomarkers (Troponin I and B-type natriuretic peptide) will also be studied; (2) To prospectively study reasons for cardiac allograft non-utilization for heart transplantation. Real-time data will be collected on specific reasons for allograft non-acceptance for transplantation in order to study graft acceptance practices and variation in graft utilization nationwide; and (3) To prospectively study associations between donor characteristics and recipient outcomes after heart transplantation. Data will be collected on recipient post-transplant length of hospitalization and survival to identify associations between donor predictors and recipient outcomes. This proposal is innovative because it focuses on an entirely different approach to donor-based research, thereby surmounting the limitations of prior investigations. Completion of the proposed study will have a positive impact by defining how to optimize the evaluation and use of available grafts for heart transplantation, thereby safely expanding the donor pool and increasing the number of heart transplants performed nationwide.

Eligibility criteria: Inclusion Criteria:

1. Brain dead (beating heart)
2. 18-65 years of age
3. HIV (-)
4. Donors authorized for research

Exclusion Criteria:

1. Donors not authorized for research
2. HIV (+)

Primary outcomes:
measure: Donor left ventricular ejection fraction, troponin, BNP, EKG changes (arrhythmias, QT prolongation, repolarization abnormalities, LVH, Q waves)
timeFrame: 5 years
measure: Identify decline codes for donor hearts not accepted for transplant
timeFrame: 5 years
measure: Create a statistical tools (e.g. risk prediction model) for donor heart acceptance
timeFrame: 5 years
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Donor Network of Arizona
state: Arizona
city: Oakland
country: United States
facility: California Transplant Donor Network
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Norcross
country: United States
facility: LifeLink
state: Georgia
city: Itasca
country: United States
facility: Gift of Hope
state: Illinois
city: Waltham
country: United States
facility: New England Organ Bank
state: Massachusetts
city: Ann Arbor
country: United States
facility: Gift of Life
state: Michigan
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Houston
country: United States
facility: LifeGift
state: Texas
Study officials:
References:
citation: Khush KK, Menza R, Nguyen J, Zaroff JG, Goldstein BA. Donor predictors of allograft use and recipient outcomes after heart transplantation. Circ Heart Fail. 2013 Mar;6(2):300-9. doi: 10.1161/CIRCHEARTFAILURE.112.000165. Epub 2013 Feb 7.
citation: Shah MR, Starling RC, Schwartz Longacre L, Mehra MR; Working Group Participants. Heart transplantation research in the next decade--a goal to achieving evidence-based outcomes: National Heart, Lung, And Blood Institute Working Group. J Am Coll Cardiol. 2012 Apr 3;59(14):1263-9. doi: 10.1016/j.jacc.2011.11.050.
citation: Chen JM, Sinha P, Rajasinghe HA, Suratwala SJ, McCue JD, McCarty MJ, Caliste X, Hauff HM, John R, Edwards NM. Do donor characteristics really matter? Short- and long-term impact of donor characteristics on recipient survival, 1995-1999. J Heart Lung Transplant. 2002 May;21(5):608-10. doi: 10.1016/s1053-2498(01)00367-9.
citation: De La Zerda DJ, Cohen O, Beygui RE, Kobashigawa J, Hekmat D, Laks H. Alcohol use in donors is a protective factor on recipients' outcome after heart transplantation. Transplantation. 2007 May 15;83(9):1214-8. doi: 10.1097/01.tp.0000261713.24244.ea.
citation: Lima B, Rajagopal K, Petersen RP, Shah AS, Soule B, Felker GM, Rogers JG, Lodge AJ, Milano CA. Marginal cardiac allografts do not have increased primary graft dysfunction in alternate list transplantation. Circulation. 2006 Jul 4;114(1 Suppl):I27-32. doi: 10.1161/CIRCULATIONAHA.105.000737.
citation: Nixon JL, Kfoury AG, Brunisholz K, Horne BD, Myrick C, Miller DV, Budge D, Bader F, Everitt M, Saidi A, Stehlik J, Schmidt TC, Alharethi R. Impact of high-dose inotropic donor support on early myocardial necrosis and outcomes in cardiac transplantation. Clin Transplant. 2012 Mar-Apr;26(2):322-7. doi: 10.1111/j.1399-0012.2011.01504.x. Epub 2011 Oct 10.
citation: Patel ND, Weiss ES, Nwakanma LU, Russell SD, Baumgartner WA, Shah AS, Conte JV. Impact of donor-to-recipient weight ratio on survival after heart transplantation: analysis of the United Network for Organ Sharing Database. Circulation. 2008 Sep 30;118(14 Suppl):S83-8. doi: 10.1161/CIRCULATIONAHA.107.756866.
citation: Smits JM, De Pauw M, de Vries E, Rahmel A, Meiser B, Laufer G, Zuckermann A. Donor scoring system for heart transplantation and the impact on patient survival. J Heart Lung Transplant. 2012 Apr;31(4):387-97. doi: 10.1016/j.healun.2011.11.005. Epub 2011 Dec 16.
citation: Weiss ES, Allen JG, Kilic A, Russell SD, Baumgartner WA, Conte JV, Shah AS. Development of a quantitative donor risk index to predict short-term mortality in orthotopic heart transplantation. J Heart Lung Transplant. 2012 Mar;31(3):266-73. doi: 10.1016/j.healun.2011.10.004. Epub 2011 Nov 16.
citation: Wever Pinzon O, Stoddard G, Drakos SG, Gilbert EM, Nativi JN, Budge D, Bader F, Alharethi R, Reid B, Selzman CH, Everitt MD, Kfoury AG, Stehlik J. Impact of donor left ventricular hypertrophy on survival after heart transplant. Am J Transplant. 2011 Dec;11(12):2755-61. doi: 10.1111/j.1600-6143.2011.03744.x. Epub 2011 Sep 11.