Thyroxine Replacement in Organ Donors

• ClinicalTrials.gov Identifier: NCT00238030
• Recruitment Status: Completed
• First Posted: October 13, 2005
• Last Update Posted: January 5, 2011
• Sponsor: Lawson Health Research Institute
• Information provided by: Lawson Health Research Institute

Tracking Information

• First Submitted Date: October 12, 2005
• First Posted Date: October 13, 2005
• Last Update Posted Date: January 5, 2011
• Study Start Date: December 2004
• Actual Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 4, 2011): Percentage of time patients require inotropic support prior to organ procurement. [ Time Frame: every hour following administration ]
• Original Primary Outcome Measures (submitted: October 12, 2005): Percentage of time patients require inotropic support prior to organ procurement.

Current Secondary Outcome Measures (submitted: January 4, 2011)

• pharmacokinetic profiles of oral vs iv T3,T4 [ Time Frame: hourly from time of administration ]
• number of organs donated [ Time Frame: total number of organs donated at time of procurement ]
• thyroid function derangements at time of brain death [ Time Frame: thyroid function q 4hrs following declaration of brain death ]

Original Secondary Outcome Measures (submitted: October 12, 2005)

• 1. pharmacokinetic profiles of oral vs iv T3,T4
• 2. number of organs donate
• 3. thryoid function derangements at time of brain death

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Thyroxine Replacement in Organ Donors
• Official Title: Efficacy and Pharmacokinetics of Oral Thyroid Replacement Therapy in Organ Donors
• 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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Brain Death

Intervention

• Drug: L-thryoxine
  2 mcg/kg iv or 2 mcg/kg po at time of enrollment
  Other Names:

  • L-thyroxine
  • Eltroxin
• Drug: iv thryoxine
  thyroxine 2 mcg/kg iv
  Other Names:

  • L-thyroxine
  • Eltroxin

Study Arms

• Active Comparator: po thyroxine
  placebo is iv
  Interventions:

  • Drug: L-thryoxine
  • Drug: iv thryoxine
• Active Comparator: iv thyroxine
  placebo is po
  Intervention: Drug: iv thryoxine

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 4, 2011): 34
• Original Enrollment (submitted: October 12, 2005): 30
• Actual Study Completion Date: October 2010
• Actual Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

1. immediate (< 4 Hrs) organ retrieval anticipated

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT00238030
• Other Study ID Numbers: R-04-298
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Dr Michael D Sharpe, London Health Sciences Centre - University Hospital
• Study Sponsor: Lawson Health Research Institute
• Collaborators: Not Provided

Investigators

• Principal Investigator: Michael D Sharpe, MD FRCPC; London Health Sciences Centre-UC+

• PRS Account: Lawson Health Research Institute
• Verification Date: January 2011