Intravenous Thyroxine for Heart-Eligible Organ Donors

Phase 3

Completed

• Conditions: Brain Death; Heart Failure
• Interventions: Drug: Thyroxine; Drug: Saline

• Registration Number: NCT04415658
• Lead Sponsor: Washington University School of Medicine

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2020-05-27
• Study First Submitted QC: 2020-05-29
• Study First Posted: 2020-06-04
• Study Start: 2020-12-01
• Primary Completion: 2022-11-06
• Study Completion: 2022-12-06
• Results First Submitted: 2023-10-18
• Status Verified: 2023-12
• Results First Submitted QC: 2023-12-18
• Last Update Submitted: 2023-12-18
• Results First Posted: 2024-01-10
• Last Update Posted: 2024-01-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 838

Inclusion Criteria

• Declared dead by neurologic criteria (brain dead)
• Authorization for organ donation and research
• On one or more vasopressors and/or inotropes

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Thyroxine	Thyroxine	Intravenous thyroxine infusion
Saline Placebo	Saline	Intravenous saline infusion

Primary Outcome Measures

Name	Time	Method
Graft Function	30 days	30-day graft survival of hearts transplanted from study donors, obtained from SRTR recipient registry
Heart Transplanted	One week	Whether heart is transplanted into living recipient

Secondary Outcome Measures

Name	Time	Method
Time Till Off Vasopressors	72 hours	Time in hours from randomization to when weaned off vasopressors (except vasopressin)
Weaned Off Vasopressors	12 hours	Weaned off vasopressors within twelve hours
Ejection Fraction	72 hours	Left ventricular ejection fraction measured on first echocardiography
Time to Order Echo	72 hours	Time till hemodynamic stability permits ordering initial echocardiogram
Lungs Transplanted	72 hours	Whether the lungs were transplanted into a living recipient

Trial Locations

Locations (14)

Lifesharing; 🇺🇸 San Diego, California, United States

Texas Organ Sharing Alliance; 🇺🇸 San Antonio, Texas, United States

Mid-America Transplant Services; 🇺🇸 Saint Louis, Missouri, United States

Midwest Transplant Network; 🇺🇸 Westwood, Kansas, United States

LifeShare of Oklahoma; 🇺🇸 Oklahoma City, Oklahoma, United States

Southwest Transplant Alliance; 🇺🇸 Dallas, Texas, United States

Donor Network of Arizona; 🇺🇸 Phoenix, Arizona, United States

LifeCenter Northwest; 🇺🇸 Bellevue, Washington, United States

DonorConnect; 🇺🇸 Murray, Utah, United States

Lifebanc; 🇺🇸 Cleveland, Ohio, United States

Donor Alliance; 🇺🇸 Denver, Colorado, United States

OurLegacy; 🇺🇸 Maitland, Florida, United States

Iowa Donor Network; 🇺🇸 North Liberty, Iowa, United States

Louisiana Organ Procurement Agency; 🇺🇸 Covington, Louisiana, United States