Thyroid and Adrenocortical Hormone Replacement in Organ Donors

Study Overview
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Brief Summary
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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: 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) 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) 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).

Official Title
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Cadaveric Organ Donor Management: Thyroid and Adrenocortical Hormone Replacement

Conditions
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Brain Death

Intervention / Treatment
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* Drug: Levothyroxine
* Drug: Methylprednisolone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levothyroxine<br>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<br> <br> |
| Experimental: Methylprednisolone<br>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<br> <br> |
| Experimental: Combination<br>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<br> <br> Drug: Methylprednisolone<br> <br> |
| No Intervention: Control<br>No levothyroxine or methylprednisolone administered. | |

What is the study measuring?
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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 |