Intravenous Thyroxine for Heart-Eligible Organ Donors

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04415658
• Other study ID #: ODRC-002
• Status: Completed
• Phase: Phase 3
• Start date: December 1, 2020
• Est. completion date: December 6, 2022

Study information

• Verified date: December 2023
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 838
• Est. completion date: December 6, 2022
• Est. primary completion date: November 6, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 55 Years

Eligibility

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)

Related Conditions & MeSH terms

• Brain Death
• Heart Failure

Intervention

Drug:
• Thyroxine
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.
• Saline
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.

Locations

Country	Name	City	State
United States	LifeCenter Northwest	Bellevue	Washington
United States	Lifebanc	Cleveland	Ohio
United States	Louisiana Organ Procurement Agency	Covington	Louisiana
United States	Southwest Transplant Alliance	Dallas	Texas
United States	Donor Alliance	Denver	Colorado
United States	OurLegacy	Maitland	Florida
United States	DonorConnect	Murray	Utah
United States	Iowa Donor Network	North Liberty	Iowa
United States	LifeShare of Oklahoma	Oklahoma City	Oklahoma
United States	Donor Network of Arizona	Phoenix	Arizona
United States	Mid-America Transplant Services	Saint Louis	Missouri
United States	Texas Organ Sharing Alliance	San Antonio	Texas
United States	Lifesharing	San Diego	California
United States	Midwest Transplant Network	Westwood	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	Mid-America Transplant

Country where clinical trial is conducted

United States, 

References & Publications (3)

Dhar R, Marklin GF, Klinkenberg WD, Wang J, Goss CW, Lele AV, Kensinger CD, Lange PA, Lebovitz DJ. Intravenous Levothyroxine for Unstable Brain-Dead Heart Donors. N Engl J Med. 2023 Nov 30;389(22):2029-2038. doi: 10.1056/NEJMoa2305969. — View Citation

Dhar R, Stahlschmidt E, Marklin G. A Randomized Trial of Intravenous Thyroxine for Brain-Dead Organ Donors With Impaired Cardiac Function. Prog Transplant. 2020 Mar;30(1):48-55. doi: 10.1177/1526924819893295. Epub 2019 Dec 5. — View Citation

Dhar R, Stahlschmidt E, Yan Y, Marklin G. A randomized trial comparing triiodothyronine (T3) with thyroxine (T4) for hemodynamically unstable brain-dead organ donors. Clin Transplant. 2019 Mar;33(3):e13486. doi: 10.1111/ctr.13486. Epub 2019 Feb 12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Total Organs Transplanted	Total number of organs transplanted (incl. lungs, liver, kidneys, heart, pancreas)	One week
Primary	Heart Transplanted	Whether heart is transplanted into living recipient	One week
Primary	Graft Function	30-day graft survival of hearts transplanted from study donors, obtained from SRTR recipient registry	30 days
Secondary	Time Till Off Vasopressors	Time in hours from randomization to when weaned off vasopressors (except vasopressin)	72 hours
Secondary	Weaned Off Vasopressors	Weaned off vasopressors within twelve hours	12 hours
Secondary	Time to Order Echo	Time till hemodynamic stability permits ordering initial echocardiogram	72 hours
Secondary	Ejection Fraction	Left ventricular ejection fraction measured on first echocardiography	72 hours
Secondary	Lungs Transplanted	Whether the lungs were transplanted into a living recipient	72 hours