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

Sponsor

Chinese Academy of Medical Sciences, Fuwai Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT03096613

Collaborator

The Luhe Teaching Hospital of the Capital Medical University (Other), Tianjin Medical University Second Hospital (Other), The First Hospital of Hebei Medical University (Other), Henan Provincial People's Hospital (Other)

124

Enrollment

Location

Arms

21.5

Anticipated Duration (Months)

5.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure Subclinical Hypothyroidism	Drug: Levothyroxine	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

124 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Apr 18, 2017

Anticipated Primary Completion Date :

Feb 1, 2019

Anticipated Study Completion Date :

Feb 1, 2019

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Distance difference of Six-minute Walk Test (6MWT) between week 24 and baseline [Within 6 months of patient enrolled]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.