@article{9cf687de57eb446b8e7633602cc862e0,
title = "A multicenter randomized placebo-controlled trial of intravenous thyroxine for heart-eligible brain-dead organ donors",
abstract = "Background: Brain death frequently induces hemodynamic instability and cardiac stunning. Impairments in cardiac performance are major contributors to hearts from otherwise eligible organ donors not being transplanted. Deficiencies in pituitary hormones (including thyroid-stimulating hormone) may contribute to hemodynamic instability, and replacement of thyroid hormone has been proposed as a means of improving stability and increasing hearts available for transplantation. Intravenous thyroxine is commonly used in donor management. However, small controlled trials have not been able to demonstrate efficacy. Methods: This multicenter study will involve organ procurement organizations (OPOs) across the country. A total of 800 heart-eligible brain-dead organ donors who require vasopressor support will be randomly assigned to intravenous thyroxine for at least 12 h or saline placebo. The primary study hypotheses are that thyroxine treatment will result in a higher proportion of hearts transplanted and that these hearts will have non-inferior function to hearts not treated with thyroxine. Additional outcome measures are the time to achieve hemodynamic stability (weaning off vasopressors) and improvement in cardiac ejection fraction on echocardiography. Discussion: This will be the largest randomized controlled study to evaluate the efficacy of thyroid hormone treatment in organ donor management. By collaborating across multiple OPOs, it will be able to enroll an adequate number of donors and be powered to definitively answer the critical question of whether intravenous thyroxine treatment increases hearts transplanted and/or provides hemodynamic benefits for donor management. Trial registration: ClinicalTrials.govNCT04415658. Registered on June 4, 2020.",
keywords = "Brain death, Donor management, Heart transplant, Organ donation, Thyroid hormone",
author = "Rajat Dhar and Dean Klinkenberg and Gary Marklin",
note = "Funding Information: We would like to acknowledge the members of the Data Safety Monitoring Committee for this trial: Krista Lentine MD, PhD (chair), and Mark Schnitzler, PhD (both at SSM Saint Louis University Transplant Center, St. Louis, MO); Farhan Zafar, MBBS (Department of Surgery, University of Cincinnati); Jon Synder, PhD, MS (Hennepin Healthcare Research Institute, Minneapolis, MN); Jason Eberl, PhD (Albert Gnaegi Center for Health Care Ethics, Saint Louis University, St. Louis, MO); and Michael Souter, MD (Harborview Medical Center, University of Washington Medical School, and Medical Director at LifeCenter Northwest, Seattle, WA). We would also like to acknowledge the three central site coordinators for the study: Emily Stahlschmidt, Coby O{\textquoteright}Sullivan, and Shannon Simpher, as well as each of the individual OPO site coordinators, who collectively ensure accurate collection of all the study-related data and ensure adherence to the study protocols and procedures. We would also like to acknowledge all the organ procurement coordinators who perform the essential functions of this study and care for each of the donors involved in the study. We would also like to thank all members of the Organ Donation Research Council at AOPO, who provided feedback and ideas in preparing this protocol. RD is the chief investigator; he conceived the study (along with GM), led the proposal and protocol development, contributed to writing the manuscript, and approved the final version for publication. GM is the co-lead investigator, conceived and refined the study design, and assisted in the development of the protocol. DK contributed to the study design including leading the statistical aspects of protocol development and is responsible for statistical aspects of the study. All authors read and approved the final manuscript. No specific funding or financial support is provided to the PIs for the performance of this study. However, administrative support will be provided by the study sponsor for the effort to coordinate the study and perform statistical analyses. The sponsor will not have access to the primary study data or be involved in its analysis or interpretation. The sponsor will also not be involved in the writing of the manuscript. The principal investigator will have final ownership over the dataset for this study. Data will be made available to any OPOs participating in the study and to other OPOs upon reasonable request. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1186/s13063-021-05797-2",
language = "English",
volume = "22",
journal = "Trials",
issn = "1745-6215",
number = "1",
}