Developing Oral LT3 Therapy for Heart Failure - HFrEF (DOT3HF-HFrEF)

University of Pennsylvania

Status and phase: Completed; Phase 2; Phase 1

Conditions: Low T3 Syndrome; Heart Failure With Reduced Ejection Fraction (HFrEF)

Treatments: Drug: Liothyronine; Other: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04112316

833681r

1R61HL146390-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

The overall goal is to determine the safety, feasibility, and preliminary efficacy of administering oral LT3 therapy in the study population of participants with Heart Failure with reduced ejection fraction (HFrEF). The study will consist of two treatment periods - each treatment period will be approximately 8 weeks in duration, with weekly titration of study drug for 4 weeks, followed by a maintenance dose for 4 weeks, then 2-week washout before crossing over to the other arm (placebo or drug). LT3 will be titrated to T3 levels.

Enrollment: 28 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Men and women aged ≥18 years
2. NYHA Class I, II or III heart failure
3. EF≤40 percent within the past year
4. An implantable cardioverter-defibrillator (ICD)
5. Stable doses of neurohormonal blockade for 30 days
6. TSH and free T4 level within the laboratory reference range and total T3 level <94 ng/dL

Exclusion criteria

1. Hypertrophic or restrictive cardiomyopathy
2. Uncorrected severe primary valvular disease
3. Arrhythmia that results in irregular heart rate
4. Inability to perform VO2max exercise testing
5. Severe lung disease, including treatment with oral steroids within past 6 months for exacerbation of obstructive lung disease or use of daytime supplemental oxygen
6. Serum creatinine > 3.0 mg/dL
7. History of cirrhosis
8. LVAD use
9. Heart failure hospitalization within past month
10. Acute coronary syndrome, coronary intervention or ablation therapy within past 2 months or cardiac surgery, percutaneous repair of a valve or septal defect repair within the past 6 months
11. Taking thyroid extract, LT4, LT3, amiodarone, or medication that affects the absorption or metabolism of thyroid hormone; gastrointestinal conditions that affect the absorption of thyroid hormone
12. If female, current or planned pregnancy within the timeframe of study participation
13. Any medical condition that in the opinion of the investigator, will interfere with the safe completion of the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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28 participants in 2 patient groups, including a placebo group

Liothyronine (LT3), then placebo

Active Comparator group

Description:

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.

Treatment:

Other: Placebo

Drug: Liothyronine

Placebo, then liothyronine

Placebo Comparator group

Description:

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.

Treatment:

Other: Placebo

Drug: Liothyronine