Intravenous Thyroxine for Heart-Eligible Organ Donors

Sponsor
Washington University School of Medicine (Other)
Overall Status
Recruiting
CT.gov ID
NCT04415658
Collaborator
Mid-America Transplant (Other)
800
Enrollment
14
Locations
2
Arms
25
Anticipated Duration (Months)
57.1
Patients Per Site
2.3
Patients Per Site Per Month

Study Details

Study Description

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

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

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 Design

Study Type:
Interventional
Anticipated Enrollment :
800 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter Randomized Placebo-Controlled Trial of Intravenous Thyroxine for Heart-Eligible Brain Dead Organ Donors
Actual Study Start Date :
Dec 1, 2020
Anticipated Primary Completion Date :
Nov 30, 2022
Anticipated Study Completion Date :
Dec 31, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: Thyroxine

Intravenous thyroxine infusion

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.

Placebo Comparator: Saline Placebo

Intravenous saline infusion

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.

Outcome Measures

Primary Outcome Measures

  1. Heart transplanted [One week]

    Whether heart is transplanted into living recipient

  2. Graft function [30 days]

    30-day graft survival of hearts transplanted from study donors

Secondary Outcome Measures

  1. Time till off vasopressors [72 hours]

    Time in hours from randomization to when weaned off vasopressors (except vasopressin)

  2. Weaned off vasopressors [12 hours]

    Weaned off vasopressors within twelve hours

  3. Time to order echo [72 hours]

    Time till hemodynamic stability permits ordering initial echocardiogram

  4. Ejection fraction [72 hours]

    Left ventricular ejection fraction measured on first echocardiography

Other Outcome Measures

  1. Total organs transplanted [One week]

    Total number of organs transplanted

Eligibility Criteria

Criteria

Ages Eligible for Study:
14 Years to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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)

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Donor Network of ArizonaPhoenixArizonaUnited States85013
2LifesharingSan DiegoCaliforniaUnited States92108
3Donor AllianceDenverColoradoUnited States80230
4OurLegacyMaitlandFloridaUnited States32751
5Iowa Donor NetworkNorth LibertyIowaUnited States52317
6Midwest Transplant NetworkWestwoodKansasUnited States66205
7Louisiana Organ Procurement AgencyCovingtonLouisianaUnited States70433
8Mid-America Transplant ServicesSaint LouisMissouriUnited States63110
9LifebancClevelandOhioUnited States44128
10LifeShare of OklahomaOklahoma CityOklahomaUnited States73132
11Southwest Transplant AllianceDallasTexasUnited States75231
12Texas Organ Sharing AllianceSan AntonioTexasUnited States78229
13DonorConnectMurrayUtahUnited States84107
14LifeCenter NorthwestBellevueWashingtonUnited States98006

Sponsors and Collaborators

  • Washington University School of Medicine
  • Mid-America Transplant

Investigators

  • Principal Investigator: Rajat Dhar, MD, Washington University School of Medicine

Study Documents (Full-Text)

More Information

Publications

Responsible Party:
Rajat Dhar, Associate Professor, Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT04415658
Other Study ID Numbers:
  • ODRC-002
First Posted:
Jun 4, 2020
Last Update Posted:
Oct 6, 2021
Last Verified:
Oct 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Keywords provided by Rajat Dhar, Associate Professor, Washington University School of Medicine
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 6, 2021