Clinical trial NCT03096613: Thyroid Hormone Replacement for Subclinical Hypothyroidism and Chronic Heart Failure (ThyroHeart-CHF)
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Heart Failure
Subclinical Hypothyroidism
Keywords: heart failure
Subclinical Hypothyroidism
levothyroxine
6-minute walk test
Lead sponsor: Chinese Academy of Medical Sciences, Fuwai Hospital
Sponsor class: OTHER
Collaborators: name: The Luhe Teaching Hospital of the Capital Medical University
name: Tianjin Medical University Second Hospital
name: The First Hospital of Hebei Medical University
name: Henan Provincial People's Hospital
First posted: 2017-03-30
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Distance difference of Six-minute Walk Test (6MWT) between week 24 and baseline
timeFrame: Within 6 months of patient enrolled
Secondary outcomes:
measure: Difference of the plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) level between week 24 and baseline
timeFrame: Within 6 months of patient enrolled
measure: Change in NYHA classification between week 24 and baseline.
timeFrame: Within 6 months of patient enrolled
measure: Composite of cardiovascular death or heart failure re-hospitalization during the 24 weeks treatment
timeFrame: Within 6 months of patient enrolled
measure: Composite of cardiovascular death, re-hospitalization for cardiovascular disease, severe arrhythmia, and stroke during the 24 weeks treatment
timeFrame: Within 6 months of patient enrolled
measure: Difference of echocardiographic and cardiac magnetic resonance imaging measures between week 24 and baseline
timeFrame: Within 6 months of patient enrolled
measure: Difference of MLHFQ between week 24 and baseline
timeFrame: Within 6 months of patient enrolled
measure: Difference of serum lipid profiles between week 24 and baseline
timeFrame: Within 6 months of patient enrolled
measure: Adverse events
timeFrame: Within 6 months of patient enrolled
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese Academy of Medical Sciences, Fuwai Hospital
state: Beijing
Study officials:
affiliation: Chinese Academy of Medical Sciences, Fuwai Hospital
name: Yi-Da Tang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.