Brain DeathPhase 1/2NCT00238030
Thyroxine Replacement in Organ Donors
A Phase 1/2 study testing L-thryoxine and iv thryoxine in people with Brain Death, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
Trial 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 Read more about this study
- Who is it for?
- Ages 16 years and olderHealthy volunteers can take part
- Conditions the study is for
- Brain Death
- What is being tested?
- L-thryoxine and iv thryoxine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteCanada
- Study dates
- Dec 2004to Oct 2010
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- Brain death criteria established
- Consent for organ donation received
Who cannot join
- 1. immediate (< 4 Hrs) organ retrieval anticipated
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy and Pharmacokinetics of Oral Thyroid Replacement Therapy in Organ Donors
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
Read the 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.
- Conditions
- Brain Death
- Being tested
- L-thryoxine, iv thryoxine
- Keywords
- organ donation, thyroid replacement
- Medical subject headings
- Brain Death
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-thryoxineDrug
Also called L-thyroxine, Eltroxin
2 mcg/kg iv or 2 mcg/kg po at time of enrollment
iv thryoxineDrug
Also called L-thyroxine, Eltroxin
thyroxine 2 mcg/kg iv
| Study group | Role | What they receive |
|---|---|---|
| po thyroxine | Active comparator | placebo is iv Receives: Drug: L-thryoxine; Drug: iv thryoxine |
| iv thyroxine | Active comparator | placebo is po Receives: Drug: iv thryoxine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of time patients require inotropic support prior to organ procurement.
Measured: every hour following administration
Secondary outcomes (3)
pharmacokinetic profiles of oral vs iv T3,T4
Measured: hourly from time of administration
number of organs donated
Measured: total number of organs donated at time of procurement
thyroid function derangements at time of brain death
Measured: thyroid function q 4hrs following declaration of brain death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2005 (estimated)
- Study startDec 2004
- Primary completionMay 2009
- Study completionOct 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Brain DeathStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Investigators
- Michael D Sharpe, MD FRCPC, Principal investigator, London Health Sciences Centre-UC+
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00238030
- Sponsor's protocol ID
- R-04-298
- Status last verified
- Jan 2011
- First submitted
- 12 Oct 2005
- Last updated
- 5 Jan 2011
- Results posted
- No
- Data monitoring committee
- No
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. doi: 10.1097/00007890-199002000-00017.
PubMed 2305461Sharpe 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.
PubMed 23884915
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Pharmacokinetics of Oral Thyroid Replacement Therapy in Organ Donors
- ClinicalTrials.gov ID
- NCT00238030
- Acronym / sponsor ID
- R-04-298
- Conditions
- Brain Death
- Keywords
- organ donation, thyroid replacement
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Study start
- Dec 2004
- Primary completion
- May 2009 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 13 Oct 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| po thyroxine | Active comparator | Drug: L-thryoxine, Drug: iv thryoxineplacebo is iv |
| iv thyroxine | Active comparator | Drug: iv thryoxineplacebo is po |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Brain death criteria established
- Consent for organ donation received
Key exclusion criteria (1 listed)
- 1. immediate (< 4 Hrs) organ retrieval anticipated
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-thryoxineAlso: L-thyroxine, Eltroxin2 mcg/kg iv or 2 mcg/kg po at time of enrollment | Drug | po thyroxine |
| iv thryoxineAlso: L-thyroxine, Eltroxinthyroxine 2 mcg/kg iv | Drug | iv thyroxine, po thyroxine |
Primary outcome
Percentage of time patients require inotropic support prior to organ procurement.
Time frame: every hour following administration
3 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jan 2011.
- Background: PubMed 2305461Novitzky 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.
- Derived from this study: PubMed 23884915Sharpe 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.
Related trials for Brain Death
Not yet recruiting
Miniature In-line Respirator
Brain Death, Respiration, Artificial
Recruiting
Amnioinfusion's Protective Effects on Respiratory and Longitudinal Pediatric Outcomes After Intrapartum Meconium Exposure
Neonatal Respiratory Distress Related Conditions, Meconium
Not yet recruitingPhase 3
Cilostazol for Prevention of Recurrent Stroke Trial
Stroke Recurrence, Myocardial Infarction
Recruiting
Study of the Link Between Structural Alterations in the Hypothalamus and Cardiac Dysautonomia in Drug-resistant Epilepsy
Epilepsy, Hypothalamus
Active, not recruiting
A Device to Prevent Unexpected Death in Epilepsy
Epilepsy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael D Sharpe, MD FRCPC principal investigator
London Health Sciences Centre-UC+
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing L-thryoxine and iv thryoxine in people with Brain Death, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jan 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of time patients require inotropic support prior to organ procurement. (time frame: every hour following administration). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00238030, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2011.