Traditional Chinese Medicine Intervention for Ischemic Cardiovascular Disease Comorbid With Diabetes Mellitus: An Efficacy Comparative Study

Overview

The population with comorbid ischemic cardiovascular disease (ICD) and diabetes mellitus (DM) has been growing rapidly, characterized by high mortality rates and frequent vascular event recurrence. DM exacerbates ischemic heart disease incidence and significantly elevates mortality in this comorbid population. Polypharmacy in these patients increases risks of adverse drug interactions and imposes substantial healthcare burdens. The pathological mechanisms of comorbidity demonstrate significant alignment with the TCM. Experimental studies indicate that Xintong Oral Liquid can ameliorate myocardial ischemia through multiple mechanisms to improve vascular endothelial function and microvascular dysfunction. This study aims to investigate the long-term effects of TCM intervention in patients with comorbid ICD and DM within 72 hours of symptom onset, and to evaluate whether the TCM treatment approach-centered on Xintong Oral Liquid within an integrated general treatment and syndrome differentiation framework-demonstrates superiority over control therapy in reducing 90-day major adverse cardiovascular and cerebrovascular events (MACCEs).

Detailed description

This study is a large-scale, real-world, prospective, multi-center, non-randomized controlled clinical trail investigating the efficacy of a TCM therapeutic strategy with Xintong Oral Liquid as the core prescription in preventing major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with Ischemic Cardiovascular Disease (ICD) complicated with Diabetes Mellitus (DM). This TCM therapeutic strategy is derived from the "toxins damaging collaterals" theory in TCM pathogenesis. All enrolled patients will receive standard treatment for ICD and DM based on the recommendations of guidelines. This study will employ natural selection grouping based on shared decision-making between physicians and patients, utilizing an open-label design with blinded endpoint assessment. An independent third-party endpoint adjudication committee will be established to conduct impartial evaluation and determination of all endpoint events. The study objective is to determine the following therapeutic effects of Xintong Oral Liquid as compared with standard treatment in the treatment of patients with ICD ccomplicated with DM: (1) 90-days incidence of the composite endpoints of major adverse cardiac and cerebrovascular events (MACCE), including cardiac death, myocardial re-infarction, emergent coronary revascularization and stroke; severe complications of STEMI (including cardiogenic shock, acute left heart failure, mechanical complications and malignant arrhythmias), in-stent thrombosis and major bleeding (Bleeding Academic Research Consortium \[BARC\] grade III and V); (2) Individual event of the 90-day primary endpoint; severe STEMI complications within 30-day treatment; target vessel failure (TVF) rate of PCI; MACCEs at 30, 180 and 365 days; follow-up assessments of SAQ-7 and EQ-5D-5L; the rate of readmission for heart failure; diabetic microangiopathy.

Interventions

• Drug Xintong Oral Liquid (Sequential Phase)
  Xintong Oral Liquid (Lunan Pharmaceutical), 10 mL tid po from week 5 to 52.
• Drug Xintong Oral Liquid (Intensive Phase)
  Xintong Oral Liquid (Lunan Pharmaceutical), 20 mL tid po for 4 weeks.
• Drug TCM Syndrome Differentiation Decoction
  Individualized herbal decoction based on TCM diagnosis (four diagnostic methods), administered for 14 days during intensive phase.
• Drug Standard Treatment (Guideline-Based)
  Combination therapy including: 1. Antiplatelet: aspirin 100 mg/day + clopidogrel 75 mg/day. 2. Lipid-lowering: atorvastatin 20 mg/day. 3. Antidiabetic: metformin 500 mg bid (max 2000 mg/day). \*Doses may be adjusted per local guidelines or patient tolerance.

Primary outcome measures

• 90-day Major Adverse Cardiovascular and Cerebrovascular Events (MACCEs) [Time frame: 90 days]

Secondary outcome measures (8)

• 30-day Severe STEMI Complications (Killip Class II-IV) [Time frame: 30 days]
• 30-day Severe Bleeding (BARC Type 3 or 5) [Time frame: 30 days]
• 365-day Target Vessel Failure (TVF) Rate [Time frame: 365 days]
• Change in LVEF (%) from Baseline to 90 days [Time frame: Baseline, 90 days]
• Change in TyG Index from Baseline to 90 days [Time frame: Baseline, 90 days]
• SAQ-7 Angina Frequency Score at baseline, 3, 6, 12 Months [Time frame: Baseline, 3, 6, 12 Months]
• EQ-5D-5L Utility Score at baseline, 3, 6, 12 Months [Time frame: Baseline, 3, 6, 12 Months]
• Heart Failure Readmission Rate at 180 Days and 365 Days [Time frame: 180 days, 365 days]

Eligibility criteria

Inclusion criteria

• Age>18 years;
• Met the diagnostic criteria for myocardial infarction and type 2 diabetes mellitus;
• Within 72 hours of myocardial infarction onset;
• Met the diagnostic criteria of "toxins damaging collaterals"；
• Voluntary participation in the study with consent forms signed.

Exclusion criteria

• Long-term (>20 min) cardio-pulmonary resuscitation (CPR);
• Critical illness due to STEMI (such as serious cardiogenic shock, uncontrolled acute left heart failure or pulmonary edema, malignant arrhythmias, explicit mechanical complications, etc. );
• Suspected aortic dissection or acute pulmonary embolism;
• Bleeding history in any organ system within 1 month, or presence of active hemorrhage at any part of the body, or known hemorrhagic constitution, or severe coagulation disorder or current usage of anticoagulants;
• Uncontrolled severe diabetic ketoacidosis;
• Serious hepatic dysfunction or serious renal dysfunction ( ALT/AST≥3 ULN or eGFR<30mL/min/1.73 m2 or equiring dialysis );
• Serious COPD or respiratory failure;
• Severe infection (such as positive blood cultures, septic shock, and septic pneumonia, etc.);
• Neuropsychiatric system diseases or unconscious and unable to cooperate with examination and treatment;
• Malignancies or other conditions with expected survival time<1 year or unsuitability to participate in this study due to other diseases;
• Allergy to the ingredients of the research drugs;
• Women who are in pregnancy or nursery;
• Participation in clinical trial of other traditional Chinese medicine.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Guangdong Traditional Chinese Medicine Hospital — Guangzhou

Identifiers

NCT: NCT07088523 · 2023ZD0505604plus

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗