Thyroid Hormone Replacement for Subclinical Hypothyroidism and Chronic Heart Failure (ThyroHeart-CHF)

Efficacy and Safety of Levothyroxine (L-T4) Replacement on Exercise Capability in Chronic Systolic Heart Failure Patients With Subclinical Hypothyroidism: A 24-week, Multi-center, Open Label, Randomized, Parallel Group Trial

Based on accumulating evidence showing that hypothyroid status is associated with poor prognosis among heart failure (HF) patients, the study is designed to evaluate whether replacement treatment with levothyroxine could have beneficial effects on patients with HF and subclinical hypothyroidism. The study is a prospective, randomized, parallel-group trial to assess the efficacy and safety of levothyroxine replacement on evidence-based HF standard therapy in stable chronic heart failure patients with subclinical hypothyroidism.

Study Overview

• Status: Unknown
• Conditions: Heart Failure; Subclinical Hypothyroidism
• Intervention / Treatment: Drug: Levothyroxine

Detailed Description

The primary objective of this trial is to determine whether the 24-week L-T4 replacement therapy, as an adjunct to standard treatment, would improve exercise capability in chronic systolic heart failure patients with subclinical hypothyroidism compared to the standard treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 124
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100037
      • Recruiting
      • Chinese Academy of Medical Sciences, Fuwai Hospital
      • Contact: Wenyao Wang, MD; Phone Number: 00861088396173; Email: wwypumc@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18 years or older, male or female.
• Systolic heart failure with New York Heart Association (NYHA) class II-III.
• Left ventricular ejection fraction (LVEF) less than 40% by echocardiography during screening and randomization.
• SCH (TSH: upper limits of normal (ULN) -10mIU/L, and FT4 level within reference range).
• Having received standard HF therapy for at least 2 weeks, having reached target dose or max tolerable dose.
• Provided informed consent.

Exclusion Criteria:

• Acute heart failure or acute exacerbation of chronic heart failure within the past 2 weeks.
• Scheduled cardiac resynchronization therapy or heart transplantation.
• History of malignant tumor or life expectancy under 12 months.
• Already on medications that may affect thyroid function (L-T4, carbimazole, propylthiouracil, amiodarone, lithium).
• Pregnancy and lactation period.
• Participation in another clinical trial within the past 30 days.
• Contraindication or intolerance to evidence-based therapy for CHF, such as beta-blocker, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.
• Known hypersensitivity to the trial treatment(s) or diluents (when applicable), including placebo or other comparator drug(s).
• Untreated adrenal insufficiency.
• Untreated pituitary insufficiency.
• Untreated thyrotoxicosis.
• Treatment with levothyroxine must not be initiated in patients with acute myocardial infarction, acute myocarditis, or acute pancarditis.
• Severe renal dysfunction (eGFR≤30 ml/min/1.73m2).
• Significant hepatic impairment (Serum GPT > 120 U/L).
• Any disorder which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Levothyroxine group; The patients allocated to levothyroxine group receive levothyroxine with a starting dose of 12.5ug.	Drug: Levothyroxine; Levothyroxine is used to normalize the thyroid hormone level of patients allocated to levothyroxine.; Other Names: Euthyrox
NO_INTERVENTION: Standard therapy group; The patients in this group receive standard therapy in consistent with the local clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Distance difference of Six-minute Walk Test (6MWT) between week 24 and baseline	Within 6 months of patient enrolled

Secondary Outcome Measures

Outcome Measure	Time Frame
Difference of the plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level between week 24 and baseline	Within 6 months of patient enrolled
Change in NYHA classification between week 24 and baseline.	Within 6 months of patient enrolled
Composite of cardiovascular death or heart failure re-hospitalization during the 24 weeks treatment	Within 6 months of patient enrolled
Composite of cardiovascular death, re-hospitalization for cardiovascular disease, severe arrhythmia, and stroke during the 24 weeks treatment	Within 6 months of patient enrolled
Difference of echocardiographic and cardiac magnetic resonance imaging measures between week 24 and baseline	Within 6 months of patient enrolled
Difference of MLHFQ between week 24 and baseline	Within 6 months of patient enrolled
Difference of serum lipid profiles between week 24 and baseline	Within 6 months of patient enrolled
Adverse events	Within 6 months of patient enrolled

Collaborators and Investigators

• Sponsor: Chinese Academy of Medical Sciences, Fuwai Hospital
• Collaborators: Henan Provincial People's Hospital; Tianjin Medical University Second Hospital; The Luhe Teaching Hospital of the Capital Medical University; The First Hospital of Hebei Medical University

Publications and helpful links

General Publications

• Zhang X, Wang WY, Zhang K, Tian J, Zheng JL, Chen J, An SM, Wang SY, Liu YP, Zhao Y, Wang JJ, Yang M, Tang YD. Efficacy and safety of levothyroxine (L-T4) replacement on the exercise capability in chronic systolic heart failure patients with subclinical hypothyroidism: Study protocol for a multi-center, open label, randomized, parallel group trial (ThyroHeart-CHF). Trials. 2019 Feb 19;20(1):143. doi: 10.1186/s13063-019-3219-5.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 18, 2017
• Primary Completion (ANTICIPATED): February 1, 2019
• Study Completion (ANTICIPATED): February 1, 2019

Study Registration Dates

• First Submitted: March 25, 2017
• First Submitted That Met QC Criteria: March 25, 2017
• First Posted (ACTUAL): March 30, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 29, 2018
• Last Update Submitted That Met QC Criteria: March 28, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: heart failure; 6-minute walk test; levothyroxine; Subclinical Hypothyroidism
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Endocrine System Diseases; Thyroid Diseases; Heart Failure; Hypothyroidism
• Other Study ID Numbers: 2016-798

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No