Clinical trial NCT04415658: Intravenous Thyroxine for Heart-Eligible Organ Donors
Official title: A Multicenter Randomized Placebo-Controlled Trial of Intravenous Thyroxine for Heart-Eligible Brain Dead Organ Donors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Brain Death
Heart Failure
Keywords: Organ donor
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Mid-America Transplant
First posted: 2020-06-04
Enrollment: 838
Sex: ALL
Minimum age (years): 14
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility 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)

Primary outcomes:
measure: Heart Transplanted
timeFrame: One week
measure: Graft Function
timeFrame: 30 days
Secondary outcomes:
measure: Time Till Off Vasopressors
timeFrame: 72 hours
measure: Weaned Off Vasopressors
timeFrame: 12 hours
measure: Time to Order Echo
timeFrame: 72 hours
measure: Ejection Fraction
timeFrame: 72 hours
measure: Lungs Transplanted
timeFrame: 72 hours
Other outcomes:
measure: Total Organs Transplanted
timeFrame: One week
Locations:
city: Phoenix
country: United States
facility: Donor Network of Arizona
state: Arizona
city: San Diego
country: United States
facility: Lifesharing
state: California
city: Denver
country: United States
facility: Donor Alliance
state: Colorado
city: Maitland
country: United States
facility: OurLegacy
state: Florida
city: North Liberty
country: United States
facility: Iowa Donor Network
state: Iowa
city: Westwood
country: United States
facility: Midwest Transplant Network
state: Kansas
city: Covington
country: United States
facility: Louisiana Organ Procurement Agency
state: Louisiana
city: Saint Louis
country: United States
facility: Mid-America Transplant Services
state: Missouri
city: Cleveland
country: United States
facility: Lifebanc
state: Ohio
city: Oklahoma City
country: United States
facility: LifeShare of Oklahoma
state: Oklahoma
city: Dallas
country: United States
facility: Southwest Transplant Alliance
state: Texas
city: San Antonio
country: United States
facility: Texas Organ Sharing Alliance
state: Texas
city: Murray
country: United States
facility: DonorConnect
state: Utah
city: Bellevue
country: United States
facility: LifeCenter Northwest
state: Washington
Study officials:
affiliation: Washington University School of Medicine
name: Rajat Dhar, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.
citation: 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.