Intravenous Thyroxine for Heart-Eligible Organ Donors
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 Disease | Intervention/Treatment | Phase |
|---|---|---|
| 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
Arms and Interventions
| Arm | Intervention/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
- Heart transplanted [One week]
Whether heart is transplanted into living recipient
- Graft function [30 days]
30-day graft survival of hearts transplanted from study donors
Secondary Outcome Measures
- 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
- Time to order echo [72 hours]
Time till hemodynamic stability permits ordering initial echocardiogram
- Ejection fraction [72 hours]
Left ventricular ejection fraction measured on first echocardiography
Other Outcome Measures
- Total organs transplanted [One week]
Total number of organs transplanted
Eligibility Criteria
Criteria
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
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Donor Network of Arizona | Phoenix | Arizona | United States | 85013 |
| 2 | Lifesharing | San Diego | California | United States | 92108 |
| 3 | Donor Alliance | Denver | Colorado | United States | 80230 |
| 4 | OurLegacy | Maitland | Florida | United States | 32751 |
| 5 | Iowa Donor Network | North Liberty | Iowa | United States | 52317 |
| 6 | Midwest Transplant Network | Westwood | Kansas | United States | 66205 |
| 7 | Louisiana Organ Procurement Agency | Covington | Louisiana | United States | 70433 |
| 8 | Mid-America Transplant Services | Saint Louis | Missouri | United States | 63110 |
| 9 | Lifebanc | Cleveland | Ohio | United States | 44128 |
| 10 | LifeShare of Oklahoma | Oklahoma City | Oklahoma | United States | 73132 |
| 11 | Southwest Transplant Alliance | Dallas | Texas | United States | 75231 |
| 12 | Texas Organ Sharing Alliance | San Antonio | Texas | United States | 78229 |
| 13 | DonorConnect | Murray | Utah | United States | 84107 |
| 14 | LifeCenter Northwest | Bellevue | Washington | United States | 98006 |
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
- 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.
- 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.
- ODRC-002