Trial Outcomes & Findings for Developing Oral LT3 Therapy for Heart Failure - HFpEF (NCT NCT04111536)

NCT ID: NCT04111536

Last Updated: 2025-01-08

Results Overview

Number 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: 2025-01-08

Participant Flow

Participant milestones

Measure	Liothyronine (LT3), Then Placebo Liothyronine (L-triiodothyronine or LT3) in the 5 mcg tablet dose formulation. Minimum LT3 dose will be 2.5 mcg three times daily and the maximum LT3 dose will be 12.5 mcg three times daily. liothyronine: Each treatment period of liothyronine was approximately 8 weeks in duration, 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 the alternate therapy - placebo. Placebo: Each treatment period of placebo was approximately 8 weeks in duration, 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 the alternate therapy - LT3.	Placebo, Then Liothyronine A placebo tablet matching in appearance to LT3 tablets, dosed equivalently. Minimum placebo tablet dose will be 1/2 tablet (2.5 mcg equivalent) three times daily and the maximum placebo dose will be 2 1/2 tablets (12.5 mcg equivalent) three times daily. liothyronine: Each treatment period of liothyronine was approximately 8 weeks in duration, 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 the alternate therapy - placebo. Placebo: Each treatment period of placebo was approximately 8 weeks in duration, 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 the alternate therapy - LT3.
First Intervention (8 Weeks) STARTED	14	14
First Intervention (8 Weeks) COMPLETED	14	12
First Intervention (8 Weeks) NOT COMPLETED	0	2
Washout (2 Weeks) STARTED	14	12
Washout (2 Weeks) COMPLETED	14	12
Washout (2 Weeks) NOT COMPLETED	0	0
Second Intervention (8 Weeks) STARTED	14	12
Second Intervention (8 Weeks) COMPLETED	13	11
Second Intervention (8 Weeks) NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Liothyronine (LT3), Then Placebo Liothyronine (L-triiodothyronine or LT3) in the 5 mcg tablet dose formulation. Minimum LT3 dose will be 2.5 mcg three times daily and the maximum LT3 dose will be 12.5 mcg three times daily. liothyronine: Each treatment period of liothyronine was approximately 8 weeks in duration, 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 the alternate therapy - placebo. Placebo: Each treatment period of placebo was approximately 8 weeks in duration, 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 the alternate therapy - LT3.	Placebo, Then Liothyronine A placebo tablet matching in appearance to LT3 tablets, dosed equivalently. Minimum placebo tablet dose will be 1/2 tablet (2.5 mcg equivalent) three times daily and the maximum placebo dose will be 2 1/2 tablets (12.5 mcg equivalent) three times daily. liothyronine: Each treatment period of liothyronine was approximately 8 weeks in duration, 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 the alternate therapy - placebo. Placebo: Each treatment period of placebo was approximately 8 weeks in duration, 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 the alternate therapy - LT3.
First Intervention (8 Weeks) Withdrawal by Subject	0	1
First Intervention (8 Weeks) Adverse Event	0	1
Second Intervention (8 Weeks) Lost to Follow-up	1	0
Second Intervention (8 Weeks) Adverse Event	0	1

Baseline Characteristics

Developing Oral LT3 Therapy for Heart Failure - HFpEF

Baseline characteristics by cohort

Measure	Liothyronine (LT3), Then Placebo n=14 Participants Liothyronine (L-triiodothyronine or LT3) in the 5 mcg tablet dose formulation. Minimum LT3 dose will be 2.5 mcg three times daily and the maximum LT3 dose will be 12.5 mcg three times daily. liothyronine: Each treatment period of liothyronine was approximately 8 weeks in duration, 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 the alternate therapy - placebo. Placebo: Each treatment period of placebo was approximately 8 weeks in duration, 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 the alternate therapy - LT3.	Placebo, Then Liothyronine n=14 Participants A placebo tablet matching in appearance to LT3 tablets, dosed equivalently. Minimum placebo tablet dose will be 1/2 tablet (2.5 mcg equivalent) three times daily and the maximum placebo dose will be 2 1/2 tablets (12.5 mcg equivalent) three times daily. liothyronine: Each treatment period of liothyronine was approximately 8 weeks in duration, 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 the alternate therapy - placebo. Placebo: Each treatment period of placebo was approximately 8 weeks in duration, 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 the alternate therapy - LT3.	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	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants	13 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=5 Participants	14 Participants n=7 Participants	28 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	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	12 Participants n=7 Participants	21 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 with atrial fibrillation or ventricular tachycardia >=4 beats

Outcome measures

Measure	Liothyronine (LT3) n=25 Participants Participants who received liothyronine for the first 8 weeks or the last 8 weeks of the study.	Placebo n=27 Participants Participants who received placebo for the first 8 weeks or the last 8 weeks of the study.
Number of Participants With Atrial Fibrillation or Ventricular Tachycardia >=4 Beats	10 Number of participants with events	12 Number of participants with events

PRIMARY outcome

Timeframe: 8 weeks

Number of participant T3 levels above upper limit of reference range

Outcome measures

Measure	Liothyronine (LT3) n=25 Participants Participants who received liothyronine for the first 8 weeks or the last 8 weeks of the study.	Placebo n=25 Participants Participants who received placebo for the first 8 weeks or the last 8 weeks of the study.
T3 Level	7 Participants	0 Participants

SECONDARY outcome

Timeframe: 8 weeks

Peak rate of oxygen consumption at 8 weeks

Outcome measures

Measure	Liothyronine (LT3) n=20 Participants Participants who received liothyronine for the first 8 weeks or the last 8 weeks of the study.	Placebo n=20 Participants Participants who received placebo for the first 8 weeks or the last 8 weeks of the study.
Peak Maximal Rate of Oxygen Consumption During Exercise (VO2 Max)	9.53 ml/kg/min Standard Deviation 3.42	10.07 ml/kg/min Standard Deviation 3.40

SECONDARY outcome

Timeframe: 8 weeks

Change in Kansas City Cardiomyopathy Questionnaire, KCCQ scale of 0 to 100, higher score is better outcome, from baseline to 8 weeks

Outcome measures

Measure	Liothyronine (LT3) n=25 Participants Participants who received liothyronine for the first 8 weeks or the last 8 weeks of the study.	Placebo n=25 Participants Participants who received placebo for the first 8 weeks or the last 8 weeks of the study.
Measure of Quality of Life	0.1 score on a scale Standard Deviation 11.5	0.5 score on a scale Standard Deviation 11.1

SECONDARY outcome

Timeframe: 8 weeks

Remotely sensed minutes/day of cumulative light, moderate or vigorous activity after 8 weeks of LT3 or placebo

Outcome measures

Measure	Liothyronine (LT3) n=24 Participants Participants who received liothyronine for the first 8 weeks or the last 8 weeks of the study.	Placebo n=25 Participants Participants who received placebo for the first 8 weeks or the last 8 weeks of the study.
Actigraphy	224 minutes/day Standard Deviation 70	230 minutes/day Standard Deviation 78

SECONDARY outcome

Timeframe: 8 weeks

Change in B-type natriuretic peptide, Pg/mL, from baseline to 8 weeks

Outcome measures

Measure	Liothyronine (LT3) n=25 Participants Participants who received liothyronine for the first 8 weeks or the last 8 weeks of the study.	Placebo n=25 Participants Participants who received placebo for the first 8 weeks or the last 8 weeks of the study.
NT-proBNP Levels	51.4 pg/mL Standard Error 187.6	8.5 pg/mL Standard Error 150.0

Adverse Events

Liothyronine (LT3)

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious 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.
Vascular disorders stroke	0.00% 0/28 • 17 weeks	3.6% 1/28 • Number of events 1 • 17 weeks
Cardiac disorders heart failure	0.00% 0/28 • 17 weeks	3.6% 1/28 • Number of events 1 • 17 weeks

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.
General disorders General	35.7% 10/28 • Number of events 18 • 17 weeks	53.6% 15/28 • Number of events 24 • 17 weeks

Additional Information

Theresa M Scattergood, MSN

University of Pennsylvania

Phone: 215-898-5664

Email: theresa.scattergood@pennmedicine.upenn.edu

Results disclosure agreements

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