Lipoic Acid in Chronic Ischemic Heart Failure: Assessment of Reduction in Major Adverse Cardiovascular Events
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 1,526
- 试验地点
- 21
- 主要终点
- Major Adverse Cardiovascular Events (MACE)
研究概览
简要总结
Chronic heart failure is a clinical condition caused by structural heart disease and is characterized by reduced pumping function, fluid retention, and abnormal activation of neurohormonal systems. It represents the advanced stage of many cardiovascular diseases and remains a major global health challenge. Despite progress in medical and interventional therapies, patients with chronic heart failure continue to experience high rates of death, hospitalization, and long-term disability.
Ischemic heart failure, which develops as a result of coronary artery disease and prior myocardial infarction, is the most common form of chronic heart failure. Current treatment strategies, including guideline-directed medical therapy and revascularization procedures, can improve symptoms and outcomes but do not fully address the residual risk of adverse cardiovascular events. Therefore, additional therapeutic approaches are needed to further improve long-term prognosis in this population.
Abnormal myocardial energy metabolism is a key pathological feature of heart failure. Mitochondria play a central role in energy production, and impaired mitochondrial function contributes to disease progression. Previous studies by our group have identified mitochondrial aldehyde dehydrogenase 2 (ALDH2) as an important regulator of myocardial metabolic homeostasis and cardiac protection under ischemic and stress conditions.
Alpha-lipoic acid is a vitamin B-related compound with antioxidant properties and has been widely used in clinical practice for other indications. Increasing evidence suggests that alpha-lipoic acid may also exert protective effects in cardiovascular diseases, potentially through modulation of mitochondrial function. Experimental studies have shown that alpha-lipoic acid can restore ALDH2 activity and improve cardiac function in models of heart failure.
Based on these findings, we conducted an exploratory randomized controlled trial between 2019 and 2023 to evaluate the safety and potential efficacy of alpha-lipoic acid in patients with ischemic heart failure. In this multicenter study, patients receiving alpha-lipoic acid showed favorable trends toward reduced risk of death and heart failure-related hospitalization, as well as significant improvements in left ventricular ejection fraction and exercise capacity, without an increase in adverse events.
Taken together, prior mechanistic research and early clinical evidence support the hypothesis that alpha-lipoic acid may provide additional benefit when used as adjunctive therapy in patients with chronic ischemic heart failure. The present study is designed to further evaluate whether long-term supplementation with alpha-lipoic acid can reduce major adverse cardiovascular events and improve clinical outcomes in this population.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 years or older and younger than 75 years at the time of enrollment.
- •A history of chronic heart failure for more than 3 months, or clinical symptoms of heart failure lasting more than 3 months, diagnosed according to the 2023 European Society of Cardiology guidelines for the diagnosis and treatment of chronic heart failure.
- •Left ventricular ejection fraction (LVEF) of 40% or less, as assessed by echocardiography.
- •A history of acute myocardial infarction more than 3 months prior to enrollment, diagnosed according to the Fourth Universal Definition of Myocardial Infarction.
- •New York Heart Association (NYHA) functional class II to IV, with stable clinical symptoms.
- •Receipt of guideline-directed medical therapy for heart failure for at least 2 weeks, without dose adjustment or intravenous therapy during this period. Guideline-directed medical therapy includes: Angiotensin-converting enzyme inhibitors (ACEIs), or Angiotensin receptor blockers (ARBs), or Angiotensin receptor-neprilysin inhibitors (ARNIs), Beta-blockers, and Mineralocorticoid receptor antagonists,unless contraindicated or not tolerated, and prescribed at optimal tolerated doses.
- •Ability and willingness to understand the study procedures and provide written informed consent.
排除标准
- •Prior cardiac resynchronization therapy (CRT).
- •Severe hepatic dysfunction, defined as liver transaminase levels greater than three times the upper limit of normal, or severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m².
- •Presence of uncontrolled malignant arrhythmias or progressively worsening unstable angina.
- •Presence of malignancy, lymphoma, leukemia, or other serious diseases with an expected life expectancy of less than 1 year.
- •Participation in another investigational drug study within 4 weeks prior to enrollment, or current receipt of any investigational treatment other than the study intervention.
- •Pregnant or breastfeeding women.
- •Known allergy to vitamin B-related medications.
研究组 & 干预措施
placebo group
干预措施: placebo (Drug)
Alpha-Lipoic Acid (ALA)
干预措施: Alpha-Lipoic Acid (ALA) (Drug)
结局指标
主要结局
Major Adverse Cardiovascular Events (MACE)
时间窗: From enrollment to the end of treatment at 24 months.
Major adverse cardiovascular events (MACE) are defined as a composite outcome that includes cardiovascular death, hospitalization for heart failure, non-fatal stroke, and non-fatal myocardial infarction occurring during the follow-up period. The primary outcome is the occurrence of the first MACE event during follow-up, identified using standard clinical criteria and confirmed through medical records.
Hospitalization for Heart Failure
时间窗: From enrollment to the end of treatment at 24 months.
Unplanned admission to the hospital due to worsening heart failure symptoms that require intravenous treatment or intensified medical care during follow-up.
次要结局
- Hospitalization for Heart Failure(From enrollment to the end of treatment at 24 months.)
- Non-fatal Stroke(From enrollment to the end of treatment at 24 months.)
- Non-fatal Myocardial Infarction(From enrollment to the end of treatment at 24 months.)
- All-cause Mortality(From enrollment to the end of treatment at 24 months.)
- Change in Left Ventricular Ejection Fraction (LVEF)(From enrollment to the end of treatment at 24 months.)
- Change in 6-Minute Walk Distance (6MWD)(From enrollment to the end of treatment at 24 months.)
- Change in NT-proBNP Level(From enrollment to the end of treatment at 24 months.)
- Change in Quality of Life Score (KCCQ)(From enrollment to the end of treatment at 24 months.)
- Unplanned Coronary Revascularization(From enrollment to the end of treatment at 24 months.)
- Heart Transplantation(From enrollment to the end of treatment at 24 months.)
研究者
Xu Lei
Dr.
Shanghai Zhongshan Hospital