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
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 124
- 试验地点
- 1
- 主要终点
- Distance difference of Six-minute Walk Test (6MWT) between week 24 and baseline
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Levothyroxine group
The patients allocated to levothyroxine group receive levothyroxine with a starting dose of 12.5ug.
干预措施: Levothyroxine (Drug)
结局指标
主要结局
Distance difference of Six-minute Walk Test (6MWT) between week 24 and baseline
时间窗: Within 6 months of patient enrolled
次要结局
- 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)
研究者
Yi-Da Tang
Professor, chief physician
Chinese Academy of Medical Sciences, Fuwai Hospital