Intravenous Thyroxine for Heart-Eligible Organ Donors

NCT04415658 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: ODRC-002
• Study Type: interventional
• Target: 838
• Locations: 1 country
• Sites: 14

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

Conditions

Brain Death; Heart Failure

Keywords

Organ donor

Outcome Measures

Primary Outcomes (2)

• Heart Transplanted

  Whether heart is transplanted into living recipient

  One week

• Graft Function

  30-day graft survival of hearts transplanted from study donors, obtained from SRTR recipient registry

  30 days

Secondary Outcomes (5)

• Time Till Off Vasopressors

  72 hours

• Weaned Off Vasopressors

  12 hours

• Time to Order Echo

  72 hours

• Ejection Fraction

  72 hours

• Lungs Transplanted

  72 hours

Other Outcomes (1)

• Total Organs Transplanted

  One week

Study Arms (2)

Thyroxine

EXPERIMENTAL

Intravenous thyroxine infusion

Drug: Thyroxine

Saline Placebo

PLACEBO COMPARATOR

Intravenous saline infusion

Drug: Saline

Interventions

Thyroxine 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.

Thyroxine

Saline 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.

Saline Placebo

Eligibility Criteria

• Age: 14 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Mid-America Transplant: collaborator

Study Sites (14)

Donor Network of Arizona

Phoenix, Arizona, 85013, United States

Location

Lifesharing

San Diego, California, 92108, United States

Location

Donor Alliance

Denver, Colorado, 80230, United States

Location

OurLegacy

Maitland, Florida, 32751, United States

Location

Iowa Donor Network

North Liberty, Iowa, 52317, United States

Location

Midwest Transplant Network

Westwood, Kansas, 66205, United States

Location

Louisiana Organ Procurement Agency

Covington, Louisiana, 70433, United States

Location

Mid-America Transplant Services

St Louis, Missouri, 63110, United States

Location

Lifebanc

Cleveland, Ohio, 44128, United States

Location

LifeShare of Oklahoma

Oklahoma City, Oklahoma, 73132, United States

Location

Southwest Transplant Alliance

Dallas, Texas, 75231, United States

Location

Texas Organ Sharing Alliance

San Antonio, Texas, 78229, United States

Location

DonorConnect

Murray, Utah, 84107, United States

Location

LifeCenter Northwest

Bellevue, Washington, 98006, United States

Location

Related Publications (4)

• 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.

  PMID: 30689222 BACKGROUND

• 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.

  PMID: 31802716 BACKGROUND

• 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.

  PMID: 38048188 BACKGROUND

• 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.

  PMID: 34838132 DERIVED

MeSH Terms

Conditions

Brain Death; Heart Failure

Interventions

Thyroxine; Sodium Chloride

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Coma; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

Not blinded, open-label use of levothyroxine permitted in control group after 12 hours (only 50 donors in that group received open-label, plus three who crossed-over to levothyroxine immediately after randomization)

Results Point of Contact

• Title: Dr. Rajat Dhar
• Organization: Washington University in St. Louis School of Medicine

dharr@wustl.edu

3143622999

Study Officials

• Rajat Dhar, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 27, 2020
• First Posted: June 4, 2020
• Study Start: December 1, 2020
• Primary Completion: November 6, 2022
• Study Completion: December 6, 2022
• Last Updated: January 10, 2024
• Results First Posted: January 10, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)