Thyroxine Replacement in Organ Donors

Study Overview
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Brief Summary
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To compare oral versus intravenous administration of thyroid hormone: 1) for reversibility of hemodynamic instability in organ donors, and, 2) the pharmacokinetics of oral vs iv thyroid administration

Detailed Description
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Disruption of the hypothalamic-pituitary axis following brain death may lead to hemodynamic instability, peripheral vasodilation, and diabetes insipidus in organ donors, requiring the use of high doses of inotropes. Inotropes may cause ischemic injury to organs and intramyocardial ATP stores, resulting in organs unsuitable for transplantation, as well as, a reduction in post-transplant organ function. Therefore, some clinicians advocate the use of triple hormonal therapy in potential organ donors. Since intravenous T3(the intracellular active form of thyroxine) is unavailable, oral or intravenous T4 must be used, requiring the conversion of T4 to T3at the cellular level. This conversion is impeded by glucocorticoids which also are administered to organ donors for their immunomodulating effects. Since oral T3 is readily available, our first question is whether oral versus intravenous administration of T4 is comparable. If so, our next study is to determine the efficacy of oral T3 versus oral T4. Our hypothesis is oral T3 is superior to oral T4. Our study therefore will determine whether or not the oral route is suitable for administration of thyroid replacement therapy. The study will compare the pharmacokinetics of oral versus intravenous T4 administration in organ donors, as well as, determine its ability to wean intropes in this patient population.

Official Title
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Efficacy and Pharmacokinetics of Oral Thyroid Replacement Therapy in Organ Donors

Conditions
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Brain Death

Intervention / Treatment
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* Drug: L-thryoxine
* Drug: iv thryoxine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Brain death criteria established Consent for organ donation received Exclusion Criteria: 1. immediate (< 4 Hrs) organ retrieval anticipated

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: po thyroxine<br>placebo is iv | Drug: L-thryoxine<br>* 2 mcg/kg iv or 2 mcg/kg po at time of enrollment<br>* Other names: Eltroxin;Drug: iv thryoxine<br>* thyroxine 2 mcg/kg iv<br>* Other names: Eltroxin;|
| Active Comparator: iv thyroxine<br>placebo is po | Drug: iv thryoxine<br>* thyroxine 2 mcg/kg iv<br>* Other names: Eltroxin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of time patients require inotropic support prior to organ procurement. |  | every hour following administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacokinetic profiles of oral vs iv T3,T4 |  | hourly from time of administration | 
| number of organs donated |  | total number of organs donated at time of procurement | 
| thyroid function derangements at time of brain death |  | thyroid function q 4hrs following declaration of brain death | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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organ donation, thyroid replacement