Intravenous Thyroxine for Heart-Eligible Organ Donors

NCT ID: NCT04415658

Last Updated: 2024-01-10

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

838 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-01

Study Completion Date

2022-12-06

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.

Conditions

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Brain Death Heart Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Thyroxine

Intravenous thyroxine infusion

Group Type EXPERIMENTAL

Thyroxine

Intervention Type DRUG

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 Placebo

Intravenous saline infusion

Group Type PLACEBO_COMPARATOR

Saline

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

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)
Minimum Eligible Age

14 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mid-America Transplant

OTHER

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Rajat Dhar

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Rajat Dhar, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

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Donor Network of Arizona

Phoenix, Arizona, United States

Site Status

Lifesharing

San Diego, California, United States

Site Status

Donor Alliance

Denver, Colorado, United States

Site Status

OurLegacy

Maitland, Florida, United States

Site Status

Iowa Donor Network

North Liberty, Iowa, United States

Site Status

Midwest Transplant Network

Westwood, Kansas, United States

Site Status

Louisiana Organ Procurement Agency

Covington, Louisiana, United States

Site Status

Mid-America Transplant Services

St Louis, Missouri, United States

Site Status

Lifebanc

Cleveland, Ohio, United States

Site Status

LifeShare of Oklahoma

Oklahoma City, Oklahoma, United States

Site Status

Southwest Transplant Alliance

Dallas, Texas, United States

Site Status

Texas Organ Sharing Alliance

San Antonio, Texas, United States

Site Status

DonorConnect

Murray, Utah, United States

Site Status

LifeCenter Northwest

Bellevue, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 30689222 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31802716 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 38048188 (View on PubMed)

Dhar R, Klinkenberg D, Marklin G. A multicenter randomized placebo-controlled trial of intravenous thyroxine for heart-eligible brain-dead organ donors. Trials. 2021 Nov 27;22(1):852. doi: 10.1186/s13063-021-05797-2.

Reference Type DERIVED
PMID: 34838132 (View on PubMed)

Provided Documents

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Document Type: Study Protocol: Appendix (Data Forms)

View Document

Document Type: Study Protocol and Statistical Analysis Plan: Study Protocol and SAP

View Document

Other Identifiers

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ODRC-002

Identifier Type: -

Identifier Source: org_study_id

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