Efficacy of Lipoic Acid on Chronic Ischemic Heart Failure Patients

Phase 3Not Yet RecruitingNCT07725484

Shanghai Zhongshan Hospital1,526 enrolled

Overview

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * 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.

Locations (21)

The First Affiliated Hospital of USTC (Anhui Provincial Hospital)

Hefei, Anhui, China

Fujian provincial hospital

Fuzhou, Fujian, China

The First Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Luoyang Central Hospital Affiliated to Zhengzhou University

Luoyang, Henan, China

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Zhongda Hospital, Southeast University

Nanjing, Jiangsu, China

Affiliated Zhongshan Hospital of Dalian University

Dalian, Liaoning, China

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, China

Qilu Hospital of Shandong University

Jinan, Shandong, China

Affiliated Hospital of Jining Medical University

Jining, Shandong, China

...and 11 more locations

Outcomes

Primary Outcomes

Major Adverse Cardiovascular Events (MACE)

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.