Thyroid and Adrenocortical Hormone Replacement in Organ Donors

Cadaveric Organ Donor Management: Thyroid and Adrenocortical Hormone Replacement

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. 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. 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. 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).

Study Overview

• Status: Completed
• Conditions: Brain Death
• Intervention / Treatment: Drug: Levothyroxine; Drug: Methylprednisolone

• Study Type: Interventional
• Enrollment (Actual): 199
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Recipients of these cadaveric organs

Exclusion Criteria:

Cadavers failing to meet inclusion criteria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levothyroxine; 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
Experimental: Methylprednisolone; 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
Experimental: Combination; 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
No Intervention: Control; No levothyroxine or methylprednisolone administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Selected graft recipient morbidity measures in all organs transplanted stratified by treatment group	90 days post transplant
Recipient Mortality	Recipient death by 90 days post transplant	90 days post traansplant

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: We Are Sharing Hope SC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2010
• Primary Completion (Actual): August 9, 2012
• Study Completion (Actual): September 30, 2013

Study Registration Dates

• First Submitted: August 20, 2020
• First Submitted That Met QC Criteria: August 24, 2020
• First Posted (Actual): August 27, 2020

Study Record Updates

• Last Update Posted (Actual): August 27, 2020
• Last Update Submitted That Met QC Criteria: August 24, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Death; Unconsciousness; Consciousness Disorders; Coma; Brain Death; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: HR 17718

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: There is currently no plan in place to share IPD for this study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No