Efficacy of Lipoic Acid on Chronic Ischemic Heart Failure Patients
Lipoic Acid in Chronic Ischemic Heart Failure: Assessment of Reduction in Major Adverse Cardiovascular Events
1 other identifier
interventional
1,526
1 country
21
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Aug 2026
Typical duration for phase_3
21 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 21, 2026
CompletedFirst Posted
Study publicly available on registry
July 24, 2026
CompletedStudy Start
First participant enrolled
August 1, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2030
July 24, 2026
July 1, 2026
4 years
July 21, 2026
July 21, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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.
From enrollment to the end of treatment at 24 months.
Hospitalization for Heart Failure
Unplanned admission to the hospital due to worsening heart failure symptoms that require intravenous treatment or intensified medical care during follow-up.
From enrollment to the end of treatment at 24 months.
Secondary Outcomes (10)
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.
- +5 more secondary outcomes
Study Arms (2)
placebo group
PLACEBO COMPARATORAlpha-Lipoic Acid (ALA)
EXPERIMENTALInterventions
After enrollment, patients received Alpha-Lipoic Acid drug at a dose of 600 mg per day for 24 months.
After enrollment, patients received placebo drug at a dose of 600 mg per day for 24 months.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (21)
The First Affiliated Hospital of USTC (Anhui Provincial Hospital)
Hefei, Anhui, 230001, China
Fujian provincial hospital
Fuzhou, Fujian, 35000, China
The First Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510080, China
Luoyang Central Hospital Affiliated to Zhengzhou University
Luoyang, Henan, 471009, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450052, China
Zhongda Hospital, Southeast University
Nanjing, Jiangsu, 210009, China
Affiliated Zhongshan Hospital of Dalian University
Dalian, Liaoning, China
The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, Shaanxi, 710061, China
Qilu Hospital of Shandong University
Jinan, Shandong, 250012, China
Affiliated Hospital of Jining Medical University
Jining, Shandong, 272029, China
The Affiliated Hospital of Qingdao University
Qingdao, Shandong, 266000, China
Zhongshan Hospital, Fudan University
Shanghai, Shanghai Municipality, 200032, China
Shanghai East Hospital, Tongji University School of Medicine
Shanghai, Shanghai Municipality, 200120, China
Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital
Shanghai, Shanghai Municipality, 200237, China
Wusong Hospital, Zhongshan Hospital, Fudan University
Shanghai, Shanghai Municipality, 200940, China
Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University
Shanghai, Shanghai Municipality, 201700, China
The Second Hospital of Shanxi Medical University
Taiyuan, Shanxi, 030001, China
Shanxi Cardiovascular Hospital
Taiyuan, Shanxi, 030024, China
Quzhou People's Hospital (Quzhou Affiliated Hospital of Wenzhou Medical University)
Quzhou, Zhejiang, 324000, China
The First Affiliated Hospital of Dalian Medical University
Dalian, China
Guangdong Provincial People's Hospital
Guangdong, China
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Dr.
Study Record Dates
First Submitted
July 21, 2026
First Posted
July 24, 2026
Study Start
August 1, 2026
Primary Completion (Estimated)
August 1, 2030
Study Completion (Estimated)
October 1, 2030
Last Updated
July 24, 2026
Record last verified: 2026-07
Data Sharing
- IPD Sharing
- Will not share
Deidentified individual participant data will not be made publicly available because the study includes sensitive clinical and genetic information, and no mechanism or participant consent for sharing data with external researchers has been established. Aggregate study results will be disseminated through ClinicalTrials.gov and peer-reviewed publications.