Trial Outcomes & Findings for Developing Oral LT3 Therapy for Heart Failure - HFrEF (NCT NCT04112316)
NCT ID: NCT04112316
Last Updated: 2024-12-24
Results Overview
Number of participants with atrial fibrillation or ventricular tachycardia \>= 4 beats
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
28 participants
Primary outcome timeframe
continuous during intervention (14 days)
Results posted on
2024-12-24
Participant Flow
Participant milestones
| Measure |
Liothyronine (LT3), Then Placebo
Participants received liothyronine first, with weekly titration of study drug for four weeks, followed by a maintenance dose for 4 weeks, then 2-week washout before crossing over to receive placebo for 8 weeks.
Liothyronine: Liothyronine (L-triiodothyronine or LT3) in the 5 mcg tablet dose formulation. Minimum LT3 dose was 2.5 mcg three times daily and the maximum LT3 dose was 12.5 mcg three times daily.
Placebo: A placebo tablet matching in appearance to LT3 tablets. Minimum placebo tablet dose was 1/2 tablet three times daily and the maximum placebo dose was 2 1/2 tablets three times daily.
|
Placebo, Then Liothyronine
Participants received placebo first, with weekly sham titration for four weeks, followed by a maintenance dose for 4 weeks, then 2-week washout before crossing over to receive LT3 for 8 weeks.
Liothyronine: Liothyronine (L-triiodothyronine or LT3) in the 5 mcg tablet dose formulation. Minimum LT3 dose was 2.5 mcg three times daily and the maximum LT3 dose was 12.5 mcg three times daily.
Placebo: A placebo tablet matching in appearance to LT3 tablets. Minimum placebo tablet dose was 1/2 tablet three times daily and the maximum placebo dose was 2 1/2 tablets three times daily.
|
|---|---|---|
|
First Period (8 Weeks)
STARTED
|
14
|
14
|
|
First Period (8 Weeks)
COMPLETED
|
12
|
14
|
|
First Period (8 Weeks)
NOT COMPLETED
|
2
|
0
|
|
Washout (2 Weeks)
STARTED
|
12
|
14
|
|
Washout (2 Weeks)
COMPLETED
|
12
|
14
|
|
Washout (2 Weeks)
NOT COMPLETED
|
0
|
0
|
|
Second Intervention (8 Weeks)
STARTED
|
12
|
14
|
|
Second Intervention (8 Weeks)
COMPLETED
|
12
|
14
|
|
Second Intervention (8 Weeks)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Liothyronine (LT3), Then Placebo
Participants received liothyronine first, with weekly titration of study drug for four weeks, followed by a maintenance dose for 4 weeks, then 2-week washout before crossing over to receive placebo for 8 weeks.
Liothyronine: Liothyronine (L-triiodothyronine or LT3) in the 5 mcg tablet dose formulation. Minimum LT3 dose was 2.5 mcg three times daily and the maximum LT3 dose was 12.5 mcg three times daily.
Placebo: A placebo tablet matching in appearance to LT3 tablets. Minimum placebo tablet dose was 1/2 tablet three times daily and the maximum placebo dose was 2 1/2 tablets three times daily.
|
Placebo, Then Liothyronine
Participants received placebo first, with weekly sham titration for four weeks, followed by a maintenance dose for 4 weeks, then 2-week washout before crossing over to receive LT3 for 8 weeks.
Liothyronine: Liothyronine (L-triiodothyronine or LT3) in the 5 mcg tablet dose formulation. Minimum LT3 dose was 2.5 mcg three times daily and the maximum LT3 dose was 12.5 mcg three times daily.
Placebo: A placebo tablet matching in appearance to LT3 tablets. Minimum placebo tablet dose was 1/2 tablet three times daily and the maximum placebo dose was 2 1/2 tablets three times daily.
|
|---|---|---|
|
First Period (8 Weeks)
Protocol Violation
|
1
|
0
|
|
First Period (8 Weeks)
Lost to Follow-up
|
1
|
0
|
Baseline Characteristics
Developing Oral LT3 Therapy for Heart Failure - HFrEF
Baseline characteristics by cohort
| Measure |
Liothyronine (LT3), Then Placebo
n=14 Participants
Participants received liothyronine first, with weekly titration of study drug for four weeks, followed by a maintenance dose for 4 weeks, then 2-week washout before crossing over to receive placebo for 8 weeks.
Liothyronine: Liothyronine (L-triiodothyronine or LT3) in the 5 mcg tablet dose formulation. Minimum LT3 dose was 2.5 mcg three times daily and the maximum LT3 dose was 12.5 mcg three times daily.
Placebo: A placebo tablet matching in appearance to LT3 tablets. Minimum placebo tablet dose was 1/2 tablet three times daily and the maximum placebo dose was 2 1/2 tablets three times daily.
|
Placebo, Then Liothyronine
n=14 Participants
Participants received placebo first, with weekly sham titration for four weeks, followed by a maintenance dose for 4 weeks, then 2-week washout before crossing over to receive LT3 for 8 weeks.
Liothyronine: Liothyronine (L-triiodothyronine or LT3) in the 5 mcg tablet dose formulation. Minimum LT3 dose was 2.5 mcg three times daily and the maximum LT3 dose was 12.5 mcg three times daily.
Placebo: A placebo tablet matching in appearance to LT3 tablets. Minimum placebo tablet dose was 1/2 tablet three times daily and the maximum placebo dose was 2 1/2 tablets three times daily.
|
Total
n=28 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
5 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
9 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Age, Continuous
|
63.9 years
STANDARD_DEVIATION 11.0 • n=5 Participants
|
59.0 years
STANDARD_DEVIATION 12.3 • n=7 Participants
|
61.4 years
STANDARD_DEVIATION 11.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
14 participants
n=5 Participants
|
14 participants
n=7 Participants
|
28 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: continuous during intervention (14 days)Number of participants with atrial fibrillation or ventricular tachycardia \>= 4 beats
Outcome measures
| Measure |
Liothyronine (LT3)
n=28 Participants
Participants who received liothyronine for the first 8 weeks or the last 8 weeks of the study.
|
Placebo
n=26 Participants
Participants who received placebo for the first 8 weeks or the last 8 weeks of the study.
|
|---|---|---|
|
Cardiac Rhythm Monitoring by 14 Day Patch Rhythm Assessment
|
11 Number of participants with events
|
19 Number of participants with events
|
PRIMARY outcome
Timeframe: 8 weeksNumber of participants with T3 levels above upper limit of reference range
Outcome measures
| Measure |
Liothyronine (LT3)
n=26 Participants
Participants who received liothyronine for the first 8 weeks or the last 8 weeks of the study.
|
Placebo
n=26 Participants
Participants who received placebo for the first 8 weeks or the last 8 weeks of the study.
|
|---|---|---|
|
T3 Level
|
4 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 8 weeksChange in peak rate of oxygen consumption during exercise between baseline and 8 weeks
Outcome measures
| Measure |
Liothyronine (LT3)
n=23 Participants
Participants who received liothyronine for the first 8 weeks or the last 8 weeks of the study.
|
Placebo
n=23 Participants
Participants who received placebo for the first 8 weeks or the last 8 weeks of the study.
|
|---|---|---|
|
Change in Peak Maximal Rate of Oxygen Consumption During Exercise (VO2 Max)
|
11.18 ml/kg/min
Standard Deviation 4.24
|
10.78 ml/kg/min
Standard Deviation 4.31
|
SECONDARY outcome
Timeframe: 8 weeksChange in KCCQ from baseline to 8 weeks, 0-100 scale, higher is better
Outcome measures
| Measure |
Liothyronine (LT3)
n=27 Participants
Participants who received liothyronine for the first 8 weeks or the last 8 weeks of the study.
|
Placebo
n=26 Participants
Participants who received placebo for the first 8 weeks or the last 8 weeks of the study.
|
|---|---|---|
|
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life
|
0.6 units on a scale
Standard Deviation 6.8
|
-0.6 units on a scale
Standard Deviation 10.3
|
SECONDARY outcome
Timeframe: 8 weeksRemotely sensed minutes/day of cumulative light, moderate, or vigorous activity in minutes/day after 8 weeks of LT3 or placebo
Outcome measures
| Measure |
Liothyronine (LT3)
n=23 Participants
Participants who received liothyronine for the first 8 weeks or the last 8 weeks of the study.
|
Placebo
n=23 Participants
Participants who received placebo for the first 8 weeks or the last 8 weeks of the study.
|
|---|---|---|
|
Activity Measured Via Actigraphy
|
241 minutes/day
Standard Deviation 83
|
265 minutes/day
Standard Deviation 82
|
SECONDARY outcome
Timeframe: 8 weeksChange in B-type natriuretic peptide levels, Pg/mL, from baseline to 8 weeks
Outcome measures
| Measure |
Liothyronine (LT3)
n=26 Participants
Participants who received liothyronine for the first 8 weeks or the last 8 weeks of the study.
|
Placebo
n=26 Participants
Participants who received placebo for the first 8 weeks or the last 8 weeks of the study.
|
|---|---|---|
|
Change in NT-proBNP Levels
|
66.1 pg/mL
Standard Deviation 248.3
|
98.7 pg/mL
Standard Deviation 450.9
|
Adverse Events
Liothyronine (LT3)
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Liothyronine (LT3)
n=28 participants at risk
Participants who received liothyronine for the first 8 weeks or the last 8 weeks of the study.
|
Placebo
n=28 participants at risk
Participants who received placebo for the first 8 weeks or the last 8 weeks of the study.
|
|---|---|---|
|
Investigations
Total
|
53.6%
15/28 • Number of events 25 • 17 weeks
|
32.1%
9/28 • Number of events 20 • 17 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place