Intravenous Thyroxine for Heart-Eligible Organ Donors

Study Overview
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Brief Summary
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This randomized controlled trial will evaluate whether intravenous thyroxine infusion given to brain-dead organ donors who are eligible to donate hearts for 12 hours will result in more hearts transplanted than saline placebo

Detailed Description
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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-hours or saline placebo. The primary study hypothesis is that thyroxine treatment results in more hearts transplanted. Additional outcome measures are 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 for 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 treatment increases hearts transplanted and/or provides other hemodynamic benefits.

Official Title
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A Multicenter Randomized Placebo-Controlled Trial of Intravenous Thyroxine for Heart-Eligible Brain Dead Organ Donors

Conditions
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Brain Death, Heart Failure

Intervention / Treatment
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* Drug: Thyroxine
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Declared dead by neurologic criteria (brain dead) Authorization for organ donation and research On one or more vasopressors and/or inotropes Exclusion Criteria: Brain death declared more than 24 hours prior Only vasopressor is vasopressin Weight < 45 kg (100 lbs) Known coronary artery disease or history of myocardial infarction Known valvular heart disease Prior sternotomy or cardiac surgery Donor at VA hospital Received intravenous or oral thyroxine within past month Known HIV+ status Other reason donor is unable to receive study drug (determined by on-site personnel)

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thyroxine<br>Intravenous thyroxine infusion | Drug: Thyroxine<br>* Infusion prepared by mixing 500 μg of drug in 500-ml of normal saline (i.e. concentration of 1 μg/ml) and enclosing the bag in an opaque sleeve. Infusion started at 30 μg/hour (30 ml/hour) for twelve hours.<br>|
| Placebo Comparator: Saline Placebo<br>Intravenous saline infusion | Drug: Saline<br>* The placebo will be a 500-ml bag of normal saline (without active drug) also enclosed in an opaque sleeve. This infusion will also be started at 30 ml/hour for twelve hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart transplanted | Whether heart is transplanted into living recipient | One week | 
| Graft function | 30-day graft survival of hearts transplanted from study donors | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time till off vasopressors | Time in hours from randomization to when weaned off vasopressors (except vasopressin) | 72 hours | 
| Weaned off vasopressors | Weaned off vasopressors within twelve hours | 12 hours | 
| Time to order echo | Time till hemodynamic stability permits ordering initial echocardiogram | 72 hours | 
| Ejection fraction | Left ventricular ejection fraction measured on first echocardiography | 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Organ donor