{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T10:30:00Z","timestamp":1756636200694,"version":"3.37.3"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,11,27]],"date-time":"2021-11-27T00:00:00Z","timestamp":1637971200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,27]],"date-time":"2021-11-27T00:00:00Z","timestamp":1637971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT04415658\">NCT04415658<\/jats:ext-link>. Registered on June 4, 2020<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13063-021-05797-2","type":"journal-article","created":{"date-parts":[[2021,11,27]],"date-time":"2021-11-27T09:02:41Z","timestamp":1638003761000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A multicenter randomized placebo-controlled trial of intravenous thyroxine for heart-eligible brain-dead organ donors"],"prefix":"10.1186","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5167-5097","authenticated-orcid":false,"given":"Rajat","family":"Dhar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dean","family":"Klinkenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Marklin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,11,27]]},"reference":[{"key":"5797_CR1","doi-asserted-by":"publisher","first-page":"S223","DOI":"10.1016\/j.healun.2004.04.005","volume":"23","author":"G Szab\u00f3","year":"2004","unstructured":"Szab\u00f3 G. 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All donors enrolled in this study have been declared dead by neurologic criteria. However, this donor management study will be approved by the research\/ethics committees at each participating OPO site. The study first received determination of non-human subjects\u2019 status from the <i>Human Research Protection Office<\/i> (HRPO) at Washington University in St. Louis (the academic affiliation of the PI). The individual OPOs will not be collecting data on recipients and so will not be engaged in human subjects\u2019 research. However, recipient outcome is a key safety endpoint for this study. The central study coordinators will use the UNOS IDs to obtain de-identified recipient outcome data through UNOS\/SRTR. As the recipients\u2019 are human subjects, in order to collect recipient outcome data, we have obtained a waiver of recipient consent from the HRPO at the coordinating site. The collection of de-identified recipient outcomes, as outlined, does not pose more than minimal risk to their privacy or safety. The study will not influence how hearts are allocated to particular recipients or means of allocation. Recipient consent would not be feasible at the time of study randomization as this occurs before heart allocation has begun, when the status of the heart and the identity of the recipient are unknown. The study intervention (T4, a standard practice in donor management) will be disclosed as part of the DonorNet platform that transplant centers\/surgeons review. Although we do not mandate that\u00a0information on the study and intervention be directly disclosed to those individuals ultimately receiving the donor hearts, this can be provided to recipients at their discretion. Furthermore,\u00a0the use of T4 (or not) is not routinely disclosed in standard practice and so this was not felt to be a significant barrier to their autonomy and decision-making. Furthermore, we will monitor for any negative impact on recipients (as a group) through our interim analysis (as overseen by the DSMC) and halt the study if one group exhibits fewer hearts transplanted or worse graft outcomes.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate {24}"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication {32}"}},{"value":"RD is a consultant for Mid-America Transplant but did not receive any support for any aspect of the study. GM is an employee of Mid-America Transplant. DK is a consultant for Mid-America Transplant, the sponsor of this study. The other authors have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests {28}"}}],"article-number":"852"}}