NCT04112316: DOT3HF-HFrEF

Developing Oral LT3 Therapy for Heart Failure - HFrEF

Completed Phase 1, PHASE2 Results posted Last updated 24 December 2024

What this trial tests

Phase 1, PHASE2 trial testing Liothyronine in Heart Failure With Reduced Ejection Fraction (HFrEF) in 28 participants. Completed in 31 October 2023.

Timeline

11 February 2020

Primary endpoint
31 October 2023

31 October 2023

Quick facts

Lead sponsor	University of Pennsylvania
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	triple
Primary purpose	treatment
Enrollment	28
Start date	11 February 2020
Primary completion	31 October 2023
Estimated completion	31 October 2023
Sites	1 location across United States

Drugs / interventions tested

• Liothyronine (LIOTHYRONINE) — full drug profile →
• Placebo

Conditions studied

• Heart Failure With Reduced Ejection Fraction (HFrEF) — all drugs for Heart Failure With Reduced Ejection Fraction (HFrEF) →
• Low T3 Syndrome — all drugs for Low T3 Syndrome →

Sponsor

University of Pennsylvania

Who can join

18 and older, any sex, with Heart Failure With Reduced Ejection Fraction (HFrEF) or Low T3 Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Cardiac Rhythm Monitoring by 14 Day Patch Rhythm Assessment Primary · continuous during intervention (14 days)

Number of participants with atrial fibrillation or ventricular tachycardia \>= 4 beats

Group	Value	95% CI
Liothyronine (LT3)	11
Placebo	19

T3 Level Primary · 8 weeks

Number of participants with T3 levels above upper limit of reference range

Group	Value	95% CI
Liothyronine (LT3)	4
Placebo	0

Change in Peak Maximal Rate of Oxygen Consumption During Exercise (VO2 Max) Secondary · 8 weeks

Change in peak rate of oxygen consumption during exercise between baseline and 8 weeks

Group	Value	95% CI
Liothyronine (LT3)	11.18	± 4.24
Placebo	10.78	± 4.31

Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life Secondary · 8 weeks

Change in KCCQ from baseline to 8 weeks, 0-100 scale, higher is better

Group	Value	95% CI
Liothyronine (LT3)	0.6	± 6.8
Placebo	-0.6	± 10.3

Activity Measured Via Actigraphy Secondary · 8 weeks

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

Group	Value	95% CI
Liothyronine (LT3)	241	± 83
Placebo	265	± 82

Change in NT-proBNP Levels Secondary · 8 weeks

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

Group	Value	95% CI
Liothyronine (LT3)	66.1	± 248.3
Placebo	98.7	± 450.9

Adverse events — posted to ClinicalTrials.gov

Time frame: 17 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Liothyronine (LT3)

Serious: 0/28 (0%)

Deaths: 0/28

Placebo

Serious: 0/28 (0%)

Deaths: 0/28

Other adverse events (1 terms — click to expand)

Reaction	System	Liothyronine (LT3)	Placebo
Total	Investigations	—	—

Data from ClinicalTrials.gov NCT04112316 adverse events section.

Sponsor's own description

Investigation of the safety, feasibility, and preliminary efficacy of thyroid hormone therapy with Liothyronine (LT3) in individuals with heart failure with reduced ejection fraction (HFrEF) and low triiodothyronine (T3) syndrome by conducting a randomized, double-blind, placebo-controlled cross-over study with a two-week washout period between treatments.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Cardiac maturation.
   Sakamoto T, Kelly DP. · · 2024 · cited 31× · PMID 38160640 · DOI 10.1016/j.yjmcc.2023.12.008