A Phase 3 interventional study of Thyroxine and Saline in Brain Death and Heart Failure, sponsored by Washington University School of Medicine. Completed at 14 sites in United States. Open to participants aged 14 Years to 55 Years. Per ClinicalTrials.gov, last updated 2024-01-10.
Sponsored by Washington University School of Medicine · Phase 3, Interventional, and Treatment
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
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.
Exclusion Criteria:
Intravenous thyroxine infusion
Drug: Thyroxine
Intravenous saline infusion
Drug: Saline
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.
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.
Heart Transplanted
Whether heart is transplanted into living recipient
Time frame: One week
Graft Function
30-day graft survival of hearts transplanted from study donors, obtained from SRTR recipient registry
Time frame: 30 days
Time Till Off Vasopressors
Time in hours from randomization to when weaned off vasopressors (except vasopressin)
Time frame: 72 hours
Weaned Off Vasopressors
Weaned off vasopressors within twelve hours
Time frame: 12 hours
Time to Order Echo
Time till hemodynamic stability permits ordering initial echocardiogram
Time frame: 72 hours
Ejection Fraction
Left ventricular ejection fraction measured on first echocardiography
Time frame: 72 hours
Lungs Transplanted
Whether the lungs were transplanted into a living recipient
Time frame: 72 hours
Total Organs Transplanted
Total number of organs transplanted (incl. lungs, liver, kidneys, heart, pancreas)
Time frame: One week
| Milestone | Thyroxine | Saline Placebo |
|---|---|---|
| Started | 419 | 419 |
| Started assigned infusion | 411 | 384 |
| Per-protocol | 351 | 374 |
| Cross-over | 0 | 3 |
| Stopped infusion early | 86 | 0 |
| Completed | 333 | 416 |
| Not completed | 86 | 3 |
| Milestone | Thyroxine | Saline Placebo |
|---|---|---|
| Started | 333 | 416 |
| Completed | 209 | 50 |
| Not completed | 124 | 366 |
Whether heart is transplanted into living recipient
| Participants | Thyroxine | Saline Placebo |
|---|---|---|
| Heart Transplanted | 230 | 223 |
30-day graft survival of hearts transplanted from study donors, obtained from SRTR recipient registry
| hearts | Thyroxine | Saline Placebo |
|---|---|---|
| Graft Function | 224 | 213 |
Time in hours from randomization to when weaned off vasopressors (except vasopressin)
| hours | Thyroxine | Saline Placebo |
|---|---|---|
| Time Till Off Vasopressors | 22 (19 to 31) | 25 (19 to 38) |
Weaned off vasopressors within twelve hours
| Participants | Thyroxine | Saline Placebo |
|---|---|---|
| Weaned Off Vasopressors | 143 | 152 |
Time till hemodynamic stability permits ordering initial echocardiogram
| hours | Thyroxine | Saline Placebo |
|---|---|---|
| Time to Order Echo | 12 (11 to 13) | 13 (12 to 14) |
Left ventricular ejection fraction measured on first echocardiography
| percentage of ejection fraction | Thyroxine | Saline Placebo |
|---|---|---|
| Ejection Fraction | 59 ± 11 | 58 ± 12 |
Whether the lungs were transplanted into a living recipient
| Participants | Thyroxine | Saline Placebo |
|---|---|---|
| Lungs Transplanted | 163 | 149 |
Total number of organs transplanted (incl. lungs, liver, kidneys, heart, pancreas)
| organs | Thyroxine | Saline Placebo |
|---|---|---|
| Total Organs Transplanted | 4 (3 to 5) | 4 (3 to 5) |
Collected over 1 week. Non-serious events are listed at a 1% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Thyroxine | 419/419 (100%) | 2/419 (0.5%) | 51/419 (12.2%) |
| Saline Placebo | 419/419 (100%) | 3/419 (0.7%) | 16/419 (3.8%) |
| Event | Thyroxine | Saline Placebo |
|---|---|---|
| Cardiac arrest / donor lossCardiac disorders | 2/419 | 3/419 |
| Event | Thyroxine | Saline Placebo |
|---|---|---|
| HypertensionCardiac disorders | 26/419 | 5/419 |
| TachycardiaCardiac disorders | 16/419 | 3/419 |
| Atrial fibrillationCardiac disorders | 7/419 | 7/419 |
| Ventricular ectopyCardiac disorders | 5/419 | 5/419 |
| Ventricular tachycardiaCardiac disorders | 4/419 | 1/419 |
| Misc/OtherGeneral disorders | 4/419 | 2/419 |
| Age, Continuous(years) | Thyroxine | Saline Placebo | Total |
|---|---|---|---|
| Mean | 36 ± 11 | 36 ± 10 | 36 ± 10 |
| Sex: Female, Male(Participants) | Thyroxine | Saline Placebo | Total |
|---|---|---|---|
| Female | 127 | 153 | 280 |
| Male | 276 | 247 | 523 |
| Race/Ethnicity, Customized(Participants) | Thyroxine | Saline Placebo | Total |
|---|---|---|---|
| White, non-Hispanic | 252 | 278 | 530 |
| Black | 75 | 49 | 124 |
| Hispanic | 60 | 63 | 123 |
| Asian, Pacific-Islander, other | 16 | 7 | 23 |
| Region of Enrollment(Participants) | Thyroxine | Saline Placebo | Total |
|---|---|---|---|
| United States | 419 | 419 | 838 |
| Blood Group(Participants) | Thyroxine | Saline Placebo | Total |
|---|---|---|---|
| O | 224 | 214 | 438 |
| A | 134 | 148 | 282 |
| B | 50 | 49 | 99 |
| AB | 11 | 8 | 19 |
| Cause of Death(Participants) | Thyroxine | Saline Placebo | Total |
|---|---|---|---|
| Anoxia | 162 | 195 | 357 |
| Stroke / Cerebrovascular | 87 | 79 | 166 |
| Trauma | 143 | 117 | 260 |
| Other | 11 | 6 | 17 |
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Washington University School of Medicine