Trial Outcomes & Findings for Intravenous Thyroxine for Heart-Eligible Organ Donors (NCT NCT04415658)

NCT ID: NCT04415658

Last Updated: 2024-01-10

Results Overview

Whether heart is transplanted into living recipient

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 838 participants
• Primary outcome timeframe: One week
• Results posted on: 2024-01-10

Participant Flow

Participant milestones

Measure	Thyroxine Intravenous thyroxine infusion Thyroxine: 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.	Saline Placebo Intravenous saline infusion Saline: 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.
Initial Study Period (12 Hours) STARTED	419	419
Initial Study Period (12 Hours) Started Assigned Infusion	411	384
Initial Study Period (12 Hours) Per-Protocol	351	374
Initial Study Period (12 Hours) Cross-over	0	3
Initial Study Period (12 Hours) Stopped Infusion Early	86	0
Initial Study Period (12 Hours) COMPLETED	333	416
Initial Study Period (12 Hours) NOT COMPLETED	86	3
Open-Label (T4 Beyond 12 Hours) STARTED	333	416
Open-Label (T4 Beyond 12 Hours) COMPLETED	209	50
Open-Label (T4 Beyond 12 Hours) NOT COMPLETED	124	366

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

missing data for 16 in T4 and 19 in NS group

Baseline characteristics by cohort

Measure	Thyroxine n=419 Participants Intravenous thyroxine infusion Thyroxine: 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.	Saline Placebo n=419 Participants Intravenous saline infusion Saline: 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.	Total n=838 Participants Total of all reporting groups
Age, Continuous	36 years STANDARD_DEVIATION 11 • n=419 Participants	36 years STANDARD_DEVIATION 10 • n=419 Participants	36 years STANDARD_DEVIATION 10 • n=838 Participants
Sex: Female, Male Female	127 Participants n=403 Participants • missing data for 16 in T4 and 19 in NS group	153 Participants n=400 Participants • missing data for 16 in T4 and 19 in NS group	280 Participants n=803 Participants • missing data for 16 in T4 and 19 in NS group
Sex: Female, Male Male	276 Participants n=403 Participants • missing data for 16 in T4 and 19 in NS group	247 Participants n=400 Participants • missing data for 16 in T4 and 19 in NS group	523 Participants n=803 Participants • missing data for 16 in T4 and 19 in NS group
Race/Ethnicity, Customized White, non-Hispanic	252 Participants n=403 Participants • Missing data on 16 in T4 and 22 in NS group	278 Participants n=397 Participants • Missing data on 16 in T4 and 22 in NS group	530 Participants n=800 Participants • Missing data on 16 in T4 and 22 in NS group
Race/Ethnicity, Customized Black	75 Participants n=403 Participants • Missing data on 16 in T4 and 22 in NS group	49 Participants n=397 Participants • Missing data on 16 in T4 and 22 in NS group	124 Participants n=800 Participants • Missing data on 16 in T4 and 22 in NS group
Race/Ethnicity, Customized Hispanic	60 Participants n=403 Participants • Missing data on 16 in T4 and 22 in NS group	63 Participants n=397 Participants • Missing data on 16 in T4 and 22 in NS group	123 Participants n=800 Participants • Missing data on 16 in T4 and 22 in NS group
Race/Ethnicity, Customized Asian, Pacific-Islander, other	16 Participants n=403 Participants • Missing data on 16 in T4 and 22 in NS group	7 Participants n=397 Participants • Missing data on 16 in T4 and 22 in NS group	23 Participants n=800 Participants • Missing data on 16 in T4 and 22 in NS group
Region of Enrollment United States	419 Participants n=419 Participants	419 Participants n=419 Participants	838 Participants n=838 Participants
Blood Group O	224 Participants n=419 Participants	214 Participants n=419 Participants	438 Participants n=838 Participants
Blood Group A	134 Participants n=419 Participants	148 Participants n=419 Participants	282 Participants n=838 Participants
Blood Group B	50 Participants n=419 Participants	49 Participants n=419 Participants	99 Participants n=838 Participants
Blood Group AB	11 Participants n=419 Participants	8 Participants n=419 Participants	19 Participants n=838 Participants
Cause of Death Anoxia	162 Participants n=403 Participants • missing demographic data for 16 in T4 and 22 in NS group	195 Participants n=397 Participants • missing demographic data for 16 in T4 and 22 in NS group	357 Participants n=800 Participants • missing demographic data for 16 in T4 and 22 in NS group
Cause of Death Stroke / Cerebrovascular	87 Participants n=403 Participants • missing demographic data for 16 in T4 and 22 in NS group	79 Participants n=397 Participants • missing demographic data for 16 in T4 and 22 in NS group	166 Participants n=800 Participants • missing demographic data for 16 in T4 and 22 in NS group
Cause of Death Trauma	143 Participants n=403 Participants • missing demographic data for 16 in T4 and 22 in NS group	117 Participants n=397 Participants • missing demographic data for 16 in T4 and 22 in NS group	260 Participants n=800 Participants • missing demographic data for 16 in T4 and 22 in NS group
Cause of Death Other	11 Participants n=403 Participants • missing demographic data for 16 in T4 and 22 in NS group	6 Participants n=397 Participants • missing demographic data for 16 in T4 and 22 in NS group	17 Participants n=800 Participants • missing demographic data for 16 in T4 and 22 in NS group

PRIMARY outcome

Timeframe: One week

Whether heart is transplanted into living recipient

Outcome measures

Measure	Thyroxine n=419 Participants Intravenous thyroxine infusion Thyroxine: 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.	Saline Placebo n=419 Participants Intravenous saline infusion Saline: 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	230 Participants	223 Participants

PRIMARY outcome

Timeframe: 30 days

Population: Only out of those hearts that were transplanted (not all study participants)

30-day graft survival of hearts transplanted from study donors, obtained from SRTR recipient registry

Outcome measures

Measure	Thyroxine n=230 hearts Intravenous thyroxine infusion Thyroxine: 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.	Saline Placebo n=223 hearts Intravenous saline infusion Saline: 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.
Graft Function	224 hearts	213 hearts

SECONDARY outcome

Timeframe: 72 hours

Population: out of those who began study infusion on vasopressors

Time in hours from randomization to when weaned off vasopressors (except vasopressin)

Outcome measures

Measure	Thyroxine n=404 Participants Intravenous thyroxine infusion Thyroxine: 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.	Saline Placebo n=385 Participants Intravenous saline infusion Saline: 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.
Time Till Off Vasopressors	22 hours Interval 19.0 to 31.0	25 hours Interval 19.0 to 38.0

SECONDARY outcome

Timeframe: 12 hours

Population: out of those who began the study infusion still on vasopressors (i.e. some had been weaned off prior to infusion)

Weaned off vasopressors within twelve hours

Outcome measures

Measure	Thyroxine n=404 Participants Intravenous thyroxine infusion Thyroxine: 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.	Saline Placebo n=388 Participants Intravenous saline infusion Saline: 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.
Weaned Off Vasopressors	143 Participants	152 Participants

SECONDARY outcome

Timeframe: 72 hours

Time till hemodynamic stability permits ordering initial echocardiogram

Outcome measures

Measure	Thyroxine n=409 Participants Intravenous thyroxine infusion Thyroxine: 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.	Saline Placebo n=385 Participants Intravenous saline infusion Saline: 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.
Time to Order Echo	12 hours Interval 11.0 to 13.0	13 hours Interval 12.0 to 14.0

SECONDARY outcome

Timeframe: 72 hours

Population: only those who had echocardiography performed after study start

Left ventricular ejection fraction measured on first echocardiography

Outcome measures

Measure	Thyroxine n=350 Participants Intravenous thyroxine infusion Thyroxine: 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.	Saline Placebo n=336 Participants Intravenous saline infusion Saline: 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.
Ejection Fraction	59 percentage of ejection fraction Standard Deviation 11	58 percentage of ejection fraction Standard Deviation 12

SECONDARY outcome

Timeframe: 72 hours

Whether the lungs were transplanted into a living recipient

Outcome measures

Measure	Thyroxine n=419 Participants Intravenous thyroxine infusion Thyroxine: 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.	Saline Placebo n=419 Participants Intravenous saline infusion Saline: 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.
Lungs Transplanted	163 Participants	149 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: One week

Total number of organs transplanted (incl. lungs, liver, kidneys, heart, pancreas)

Outcome measures

Measure	Thyroxine n=419 Participants Intravenous thyroxine infusion Thyroxine: 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.	Saline Placebo n=419 Participants Intravenous saline infusion Saline: 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.
Total Organs Transplanted	4 organs Interval 3.0 to 5.0	4 organs Interval 3.0 to 5.0

Adverse Events

Thyroxine

Serious events: 2 serious events

Other events: 51 other events

Deaths: 419 deaths

Saline Placebo

Serious events: 3 serious events

Other events: 16 other events

Deaths: 419 deaths

Serious adverse events

Measure	Thyroxine n=419 participants at risk Intravenous thyroxine infusion Thyroxine: 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. Donors were followed till organ recovery or end of management.	Saline Placebo n=419 participants at risk Intravenous saline infusion Saline: 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. Donors were followed till organ recovery or end of management.
Cardiac disorders Cardiac arrest / donor loss	0.48% 2/419 • Number of events 2 • 1 week Serious adverse event defined as donor instability resulting in cardiac arrest or premature donor loss. Adverse events were collected for each arm combining all study periods, i.e. from study onset through end of donor management (organ recovery). These were not collected for each period (i.e. first 12 hours versus open-label period) separately.	0.72% 3/419 • Number of events 3 • 1 week Serious adverse event defined as donor instability resulting in cardiac arrest or premature donor loss. Adverse events were collected for each arm combining all study periods, i.e. from study onset through end of donor management (organ recovery). These were not collected for each period (i.e. first 12 hours versus open-label period) separately.

Other adverse events

Measure	Thyroxine n=419 participants at risk Intravenous thyroxine infusion Thyroxine: 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. Donors were followed till organ recovery or end of management.	Saline Placebo n=419 participants at risk Intravenous saline infusion Saline: 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. Donors were followed till organ recovery or end of management.
Cardiac disorders Tachycardia	3.8% 16/419 • Number of events 16 • 1 week Serious adverse event defined as donor instability resulting in cardiac arrest or premature donor loss. Adverse events were collected for each arm combining all study periods, i.e. from study onset through end of donor management (organ recovery). These were not collected for each period (i.e. first 12 hours versus open-label period) separately.	0.72% 3/419 • Number of events 3 • 1 week Serious adverse event defined as donor instability resulting in cardiac arrest or premature donor loss. Adverse events were collected for each arm combining all study periods, i.e. from study onset through end of donor management (organ recovery). These were not collected for each period (i.e. first 12 hours versus open-label period) separately.
Cardiac disorders Hypertension	6.2% 26/419 • Number of events 26 • 1 week Serious adverse event defined as donor instability resulting in cardiac arrest or premature donor loss. Adverse events were collected for each arm combining all study periods, i.e. from study onset through end of donor management (organ recovery). These were not collected for each period (i.e. first 12 hours versus open-label period) separately.	1.2% 5/419 • Number of events 5 • 1 week Serious adverse event defined as donor instability resulting in cardiac arrest or premature donor loss. Adverse events were collected for each arm combining all study periods, i.e. from study onset through end of donor management (organ recovery). These were not collected for each period (i.e. first 12 hours versus open-label period) separately.
Cardiac disorders Atrial fibrillation	1.7% 7/419 • Number of events 7 • 1 week Serious adverse event defined as donor instability resulting in cardiac arrest or premature donor loss. Adverse events were collected for each arm combining all study periods, i.e. from study onset through end of donor management (organ recovery). These were not collected for each period (i.e. first 12 hours versus open-label period) separately.	1.7% 7/419 • Number of events 7 • 1 week Serious adverse event defined as donor instability resulting in cardiac arrest or premature donor loss. Adverse events were collected for each arm combining all study periods, i.e. from study onset through end of donor management (organ recovery). These were not collected for each period (i.e. first 12 hours versus open-label period) separately.
Cardiac disorders Ventricular ectopy	1.2% 5/419 • Number of events 5 • 1 week Serious adverse event defined as donor instability resulting in cardiac arrest or premature donor loss. Adverse events were collected for each arm combining all study periods, i.e. from study onset through end of donor management (organ recovery). These were not collected for each period (i.e. first 12 hours versus open-label period) separately.	1.2% 5/419 • Number of events 5 • 1 week Serious adverse event defined as donor instability resulting in cardiac arrest or premature donor loss. Adverse events were collected for each arm combining all study periods, i.e. from study onset through end of donor management (organ recovery). These were not collected for each period (i.e. first 12 hours versus open-label period) separately.
Cardiac disorders Ventricular tachycardia	0.95% 4/419 • Number of events 4 • 1 week Serious adverse event defined as donor instability resulting in cardiac arrest or premature donor loss. Adverse events were collected for each arm combining all study periods, i.e. from study onset through end of donor management (organ recovery). These were not collected for each period (i.e. first 12 hours versus open-label period) separately.	0.24% 1/419 • Number of events 1 • 1 week Serious adverse event defined as donor instability resulting in cardiac arrest or premature donor loss. Adverse events were collected for each arm combining all study periods, i.e. from study onset through end of donor management (organ recovery). These were not collected for each period (i.e. first 12 hours versus open-label period) separately.
General disorders Misc/Other	0.95% 4/419 • Number of events 4 • 1 week Serious adverse event defined as donor instability resulting in cardiac arrest or premature donor loss. Adverse events were collected for each arm combining all study periods, i.e. from study onset through end of donor management (organ recovery). These were not collected for each period (i.e. first 12 hours versus open-label period) separately.	0.48% 2/419 • Number of events 2 • 1 week Serious adverse event defined as donor instability resulting in cardiac arrest or premature donor loss. Adverse events were collected for each arm combining all study periods, i.e. from study onset through end of donor management (organ recovery). These were not collected for each period (i.e. first 12 hours versus open-label period) separately.

Additional Information

Dr. Rajat Dhar

Washington University in St. Louis School of Medicine

Phone: 3143622999

Email: dharr@wustl.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place