Clinical trial NCT00238030: Thyroxine Replacement in Organ Donors
Official title: Efficacy and Pharmacokinetics of Oral Thyroid Replacement Therapy in Organ Donors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Brain Death
Keywords: organ donation
thyroid replacement
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2005-10-13
Enrollment: 34
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Brain death criteria established
2. Consent for organ donation received

Exclusion Criteria:

1. immediate (\< 4 Hrs) organ retrieval anticipated

Primary outcomes:
measure: Percentage of time patients require inotropic support prior to organ procurement.
timeFrame: every hour following administration
Secondary outcomes:
measure: pharmacokinetic profiles of oral vs iv T3,T4
timeFrame: hourly from time of administration
measure: number of organs donated
timeFrame: total number of organs donated at time of procurement
measure: thyroid function derangements at time of brain death
timeFrame: thyroid function q 4hrs following declaration of brain death
Other outcomes:
Locations:
city: London
country: Canada
facility: London Health Sciences Centre-UC
state: Ontario
Study officials:
affiliation: London Health Sciences Centre-UC+
name: Michael D Sharpe, MD FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Novitzky D, Cooper DK, Chaffin JS, Greer AE, DeBault LE, Zuhdi N. Improved cardiac allograft function following triiodothyronine therapy to both donor and recipient. Transplantation. 1990 Feb;49(2):311-6. doi: 10.1097/00007890-199002000-00017.
citation: Sharpe MD, van Rassel B, Haddara W. Oral and intravenous thyroxine (T4) achieve comparable serum levels for hormonal resuscitation protocol in organ donors: a randomized double-blinded study. Can J Anaesth. 2013 Oct;60(10):998-1002. doi: 10.1007/s12630-013-0004-x. Epub 2013 Jul 25.