Thyroid and Adrenocortical Hormone Replacement in Organ Donors

NCT04528797 | Completed

• 1 other identifier: HR 17718
• Study Type: interventional
• Target: 199
• Locations: 0 countries
• Sites: N/A

Brief Summary

Brain death inevitably leads to hemodynamic instability and prolonged hypotension that compromises viability of potentially transplantable organs. In addition to depletion of peripheral norepinephrine stores, concomitant depletion of thyroid hormone and cortisol levels are believed to contribute to this instability. Catecholamine vasopressors are widely used to support hemodynamics in potential organ donors, however their use has also been shown to compromise allograft function. Trials studying the effects of thyroid hormone and corticosteroid treatment on brain dead organ donors have had mixed results with respect to improving donor hemodynamics. Further, few studies have attempted to discriminate the relative contribution of thyroid hormone vs. corticosteroids. The specific aims of this study include:

1. 1.To quantify hemodynamic changes during the management of cadaveric organ donors routinely receiving thyroid hormone therapy alone vs. corticosteroid therapy alone vs. the combination, compared to those who do not receive any hormonal therapy (controls)
2. 2.To document number and types of organs procured in donors treated with thyroid hormone therapy alone vs. corticosteroid therapy alone vs. the combination, compared to those not treated with hormonal therapy (controls)
3. 3.To quantify graft and patient outcomes in recipients of organs exposed to thyroid hormone therapy alone vs. corticosteroid therapy alone vs. the combination, compared to recipients of organs not exposed to hormonal therapy (controls).

Conditions

Brain Death

Outcome Measures

Primary Outcomes (1)

• Change in Vasoactive Inotrope Score (VIS) score from beginning of active donor management until procurement.

  The VIS score includes all commonly used vasopressor and inotrope agents, weighted by potency and summed

  From baseline (t0) = beginning of active donor management to procurement (tOR) = time of organ procurement, up to 50 hours

Secondary Outcomes (3)

• Proportion of organs procured vs. consented, stratified by treatment group

  assessed at time of procurement, up to 50 hours following consent for donation

• Recipient Morbidity

  90 days post transplant

• Recipient Mortality

  90 days post traansplant

Study Arms (4)

Levothyroxine

EXPERIMENTAL

Levothyroxine 20 mcg IV bolus initiated at the beginning of active donor management followed by continuous infusion of 50 to 200 mcg/hr titrated to minimize vasopressor requirements until organ procurement.

Drug: Levothyroxine

Methylprednisolone

EXPERIMENTAL

Methylprednsiolone 30 mg/kg (up to 2 g) IV initiated at the beginning of active donor management followed by repeat dosing of 15 mg/kg (up to 1 g) 12 hours later.

Drug: Methylprednisolone

Combination

EXPERIMENTAL

Methylprednsiolone 30 mg/kg (up to 2 g) IV initiated at the beginning of active donor management followed by repeat dosing of 15 mg/kg (up to 1 g) 12 hours later plus levothyroxine 20 mcg IV bolus initiated at the beginning of active donor management followed by continuous infusion of 50 to 200 mcg/hr titrated to minimize vasopressor requirements until organ procurement.

Drug: Levothyroxine; Drug: Methylprednisolone

Control

NO INTERVENTION

No levothyroxine or methylprednisolone administered.

Interventions

Levothyroxine DRUG

Combination; Levothyroxine

Methylprednisolone DRUG

Combination; Methylprednisolone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cadaveric organ donors ≥ age 18 having valid consent (by advance directive or by familial consent) to donate organs.
• Recipients of these cadaveric organs

Sponsors & Collaborators

• Medical University of South Carolina: lead
• We Are Sharing Hope SC: collaborator

Related Publications (1)

• Van Bakel AB, Hino SA, Welker D, Morella K, Gregoski MJ, Craig ML, Crumbley AJ, Sade RM. Hemodynamic Effects of High-dose Levothyroxine and Methylprednisolone in Brain-dead Potential Organ Donors. Transplantation. 2022 Aug 1;106(8):1677-1689. doi: 10.1097/TP.0000000000004072. Epub 2022 Jul 22.

  PMID: 35389961 DERIVED

MeSH Terms

Conditions

Brain Death

Interventions

Thyroxine; Methylprednisolone

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

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; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: August 20, 2020
• First Posted: August 27, 2020
• Study Start: September 2, 2010
• Primary Completion: August 9, 2012
• Study Completion: September 30, 2013
• Last Updated: August 27, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share