Brain DeathPhase 3NCT04415658
Intravenous Thyroxine for Heart-Eligible Organ Donors
A Phase 3 study testing Thyroxine and Saline in people with Brain Death and Heart Failure, run by Washington University School of Medicine at 14 sites in United States.
Trial summary
This randomized controlled trial will evaluate whether intravenous thyroxine infusion given to brain-dead organ donors who are eligible to donate hearts for 12 hours will result in more hearts transplanted than saline placebo Read more about this study
- Who is it for?
- Ages 14 to 55 years
- Conditions the study is for
- Brain Death, Heart Failure
- What is being tested?
- Thyroxine and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 838 participants
- Where
- 14 sitesUnited States
- Study dates
- 1 Dec 2020to 6 Dec 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 14 to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Declared dead by neurologic criteria (brain dead)
- Authorization for organ donation and research
- On one or more vasopressors and/or inotropes
Who cannot join
- Brain death declared more than 24 hours prior
- Only vasopressor is vasopressin
- Weight < 45 kg (100 lbs)
- Known coronary artery disease or history of myocardial infarction
- Known valvular heart disease
- Prior sternotomy or cardiac surgery
Show all 10Show fewer
- Donor at VA hospital
- Received intravenous or oral thyroxine within past month
- Known HIV+ status
- Other reason donor is unable to receive study drug (determined by on-site personnel)
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
LifeCenter Northwest
Bellevue, Washington, 98006
Lifebanc
Cleveland, Ohio, 44128
Louisiana Organ Procurement Agency
Covington, Louisiana, 70433
Southwest Transplant Alliance
Dallas, Texas, 75231
Donor Alliance
Denver, Colorado, 80230
OurLegacy
Maitland, Florida, 32751
DonorConnect
Murray, Utah, 84107
Iowa Donor Network
North Liberty, Iowa, 52317
LifeShare of Oklahoma
Oklahoma City, Oklahoma, 73132
Donor Network of Arizona
Phoenix, Arizona, 85013
Texas Organ Sharing Alliance
San Antonio, Texas, 78229
Lifesharing
San Diego, California, 92108
Mid-America Transplant Services
St Louis, Missouri, 63110
Midwest Transplant Network
Westwood, Kansas, 66205
About this study
Official title: A Multicenter Randomized Placebo-Controlled Trial of Intravenous Thyroxine for Heart-Eligible Brain Dead Organ Donors
This randomized controlled trial will evaluate whether intravenous thyroxine infusion given to brain-dead organ donors who are eligible to donate hearts for 12 hours will result in more hearts transplanted than saline placebo
Read the detailed description
Background: Brain death frequently induces hemodynamic instability and cardiac stunning. Impairments in cardiac performance are major contributors to hearts from otherwise eligible organ donors not being transplanted. Deficiencies in pituitary hormones (including thyroid stimulating hormone) may contribute to hemodynamic instability and replacement of thyroid hormone has been proposed as a means of improving stability and increasing hearts available for transplantation. Intravenous thyroxine is commonly used in donor management. However, small controlled trials have not been able to demonstrate efficacy.
Methods: This multicenter study will involve organ procurement organizations (OPOs) across the country. A total of 800 heart-eligible brain dead organ donors who require vasopressor support will be randomly assigned to intravenous thyroxine for at least 12-hours or saline placebo. The primary study hypothesis is that thyroxine treatment results in more hearts transplanted. Additional outcome measures are time to achieve hemodynamic stability (weaning off vasopressors) and improvement in cardiac ejection fraction on echocardiography.
Discussion: This will be the largest randomized controlled study to evaluate the efficacy of thyroid hormone treatment for organ donor management. By collaborating across multiple OPOs, it will be able to enroll an adequate number of donors and be powered to definitively answer the critical question of whether treatment increases hearts transplanted and/or provides other hemodynamic benefits.
- Conditions
- Brain Death, Heart Failure
- Being tested
- Thyroxine, Saline
- Keywords
- Organ donor
- Medical subject headings
- Brain Death, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThyroxineDrug
Infusion prepared by mixing 500 μg of drug in 500-ml of normal saline (i.e. concentration of 1 μg/ml) and enclosing the bag in an opaque sleeve. Infusion started at 30 μg/hour (30 ml/hour) for twelve hours.
SalineDrug
The placebo will be a 500-ml bag of normal saline (without active drug) also enclosed in an opaque sleeve. This infusion will also be started at 30 ml/hour for twelve hours.
| Study group | Role | What they receive |
|---|---|---|
| Thyroxine | Experimental | Intravenous thyroxine infusion Receives: Drug: Thyroxine |
| Saline Placebo | Placebo comparator | Intravenous saline infusion Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heart Transplanted
Whether heart is transplanted into living recipient
Measured: One week
Graft Function
30-day graft survival of hearts transplanted from study donors, obtained from SRTR recipient registry
Measured: 30 days
Secondary outcomes (5)
Time Till Off Vasopressors
Time in hours from randomization to when weaned off vasopressors (except vasopressin)
Measured: 72 hours
Weaned Off Vasopressors
Weaned off vasopressors within twelve hours
Measured: 12 hours
Time to Order Echo
Time till hemodynamic stability permits ordering initial echocardiogram
Measured: 72 hours
Ejection Fraction
Left ventricular ejection fraction measured on first echocardiography
Measured: 72 hours
Lungs Transplanted
Whether the lungs were transplanted into a living recipient
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2020
- Study start1 Dec 2020
- Primary completion6 Nov 2022
- Study completion6 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Brain DeathStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 838 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Mid-America Transplant
- Responsible party
- Principal investigator, Rajat Dhar, Washington University School of Medicine
- Investigators
- Rajat Dhar, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04415658
- Sponsor's protocol ID
- ODRC-002
- Status last verified
- Dec 2023
- First submitted
- 27 May 2020
- Last updated
- 10 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Researchers within the study consortium only
Publications
Dhar R, Stahlschmidt E, Yan Y, Marklin G. A randomized trial comparing triiodothyronine (T3) with thyroxine (T4) for hemodynamically unstable brain-dead organ donors. Clin Transplant. 2019 Mar;33(3):e13486. doi: 10.1111/ctr.13486. Epub 2019 Feb 12.
PubMed 30689222Dhar R, Stahlschmidt E, Marklin G. A Randomized Trial of Intravenous Thyroxine for Brain-Dead Organ Donors With Impaired Cardiac Function. Prog Transplant. 2020 Mar;30(1):48-55. doi: 10.1177/1526924819893295. Epub 2019 Dec 5.
PubMed 31802716Dhar R, Marklin GF, Klinkenberg WD, Wang J, Goss CW, Lele AV, Kensinger CD, Lange PA, Lebovitz DJ. Intravenous Levothyroxine for Unstable Brain-Dead Heart Donors. N Engl J Med. 2023 Nov 30;389(22):2029-2038. doi: 10.1056/NEJMoa2305969.
PubMed 38048188Dhar R, Klinkenberg D, Marklin G. A multicenter randomized placebo-controlled trial of intravenous thyroxine for heart-eligible brain-dead organ donors. Trials. 2021 Nov 27;22(1):852. doi: 10.1186/s13063-021-05797-2.
PubMed 34838132
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Randomized Placebo-Controlled Trial of Intravenous Thyroxine for Heart-Eligible Brain Dead Organ Donors
- ClinicalTrials.gov ID
- NCT04415658
- Acronym / sponsor ID
- ODRC-002
- Conditions
- Brain Death, Heart Failure
- Keywords
- Organ donor
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 838 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Mid-America Transplant
- Study start
- 1 Dec 2020 (actual)
- Primary completion
- 6 Nov 2022 (actual)
- Study completion
- 6 Dec 2022 (actual)
- First posted
- 4 Jun 2020 (actual)
- Results
- Posted 10 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized controlled trial will evaluate whether intravenous thyroxine infusion given to brain-dead organ donors who are eligible to donate hearts for 12 hours will result in more hearts transplanted than saline placebo
Detailed description
Background: Brain death frequently induces hemodynamic instability and cardiac stunning. Impairments in cardiac performance are major contributors to hearts from otherwise eligible organ donors not being transplanted. Deficiencies in pituitary hormones (including thyroid stimulating hormone) may contribute to hemodynamic instability and replacement of thyroid hormone has been proposed as a means of improving stability and increasing hearts available for transplantation. Intravenous thyroxine is commonly used in donor management. However, small controlled trials have not been able to demonstrate efficacy.
Methods: This multicenter study will involve organ procurement organizations (OPOs) across the country. A total of 800 heart-eligible brain dead organ donors who require vasopressor support will be randomly assigned to intravenous thyroxine for at least 12-hours or saline placebo. The primary study hypothesis is that thyroxine treatment results in more hearts transplanted. Additional outcome measures are time to achieve hemodynamic stability (weaning off vasopressors) and improvement in cardiac ejection fraction on echocardiography.
Discussion: This will be the largest randomized controlled study to evaluate the efficacy of thyroid hormone treatment for organ donor management. By collaborating across multiple OPOs, it will be able to enroll an adequate number of donors and be powered to definitively answer the critical question of whether treatment increases hearts transplanted and/or provides other hemodynamic benefits.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Thyroxine | Experimental | Drug: ThyroxineIntravenous thyroxine infusion |
| Saline Placebo | Placebo comparator | Drug: SalineIntravenous saline infusion |
Who may qualify
- Ages
- 14 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Declared dead by neurologic criteria (brain dead)
- Authorization for organ donation and research
- On one or more vasopressors and/or inotropes
Key exclusion criteria (10 listed)
- Brain death declared more than 24 hours prior
- Only vasopressor is vasopressin
- Weight < 45 kg (100 lbs)
- Known coronary artery disease or history of myocardial infarction
- Known valvular heart disease
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 |
|---|---|---|
| ThyroxineInfusion prepared by mixing 500 μg of drug in 500-ml of normal saline (i.e. concentration of 1 μg/ml) and enclosing the bag in an opaque sleeve. Infusion started at 30 μg/hour (30 ml/hour) for twelve hours. | Drug | Thyroxine |
| SalineThe placebo will be a 500-ml bag of normal saline (without active drug) also enclosed in an opaque sleeve. This infusion will also be started at 30 ml/hour for twelve hours. | Drug | Saline Placebo |
Primary outcome
Heart Transplanted
Time frame: One week
Whether heart is transplanted into living recipient
Graft Function
Time frame: 30 days
30-day graft survival of hearts transplanted from study donors, obtained from SRTR recipient registry
5 secondary outcomes
Time Till Off Vasopressors
Time frame: 72 hours
Weaned Off Vasopressors
Time frame: 12 hours
Time to Order Echo
Time frame: 72 hours
Ejection Fraction
Time frame: 72 hours
Lungs Transplanted
Time frame: 72 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 30689222Dhar R, Stahlschmidt E, Yan Y, Marklin G. A randomized trial comparing triiodothyronine (T3) with thyroxine (T4) for hemodynamically unstable brain-dead organ donors. Clin Transplant. 2019 Mar;33(3):e13486. doi: 10.1111/ctr.13486. Epub 2019 Feb 12.
- Background: PubMed 31802716Dhar R, Stahlschmidt E, Marklin G. A Randomized Trial of Intravenous Thyroxine for Brain-Dead Organ Donors With Impaired Cardiac Function. Prog Transplant. 2020 Mar;30(1):48-55. doi: 10.1177/1526924819893295. Epub 2019 Dec 5.
- Background: PubMed 38048188Dhar R, Marklin GF, Klinkenberg WD, Wang J, Goss CW, Lele AV, Kensinger CD, Lange PA, Lebovitz DJ. Intravenous Levothyroxine for Unstable Brain-Dead Heart Donors. N Engl J Med. 2023 Nov 30;389(22):2029-2038. doi: 10.1056/NEJMoa2305969.
- Derived from this study: PubMed 34838132Dhar R, Klinkenberg D, Marklin G. A multicenter randomized placebo-controlled trial of intravenous thyroxine for heart-eligible brain-dead organ donors. Trials. 2021 Nov 27;22(1):852. doi: 10.1186/s13063-021-05797-2.
- Individual participant dataSharing planned: No. Researchers within the study consortium only
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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.
Rajat Dhar, MD principal investigator
Washington University School of Medicine
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Thyroxine and Saline in people with Brain Death and Heart Failure, run by Washington University School of Medicine at 14 sites in United States.
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 3 inclusion and 10 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 10 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Heart Transplanted (time frame: One week). The study lists 2 primary outcomes in all. 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 NCT04415658, which also lists 4 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 10 Jan 2024.