Diabete Mellitus, Ischemic Cardiovascular Disease
Conditions
Keywords
Diabete Mellitus, Ischemic cardiovascular disease, real-world, Xintong Oral Liquid
Brief summary
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
DRUGXintong Oral Liquid (Sequential Phase)
Xintong Oral Liquid (Lunan Pharmaceutical), 10 mL tid po from week 5 to 52.
DRUGXintong Oral Liquid (Intensive Phase)
Xintong Oral Liquid (Lunan Pharmaceutical), 20 mL tid po for 4 weeks.
Individualized herbal decoction based on TCM diagnosis (four diagnostic methods), administered for 14 days during intensive phase.
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.
Sponsors
Guangzhou University of Traditional Chinese Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 90-day Major Adverse Cardiovascular and Cerebrovascular Events (MACCEs) | 90 days | Composite of: 1) Myocardial re-infarction (Third Universal Definition of MI); 2) Emergent coronary revascularization; 3) Stroke (NIHSS ≥1, imaging-confirmed); 4) Cardiovascular death (adjudicated by endpoint committee). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 365-day Target Vessel Failure (TVF) Rate | 365 days | Composite of: 1) Cardiac death; 2) Target vessel myocardial infarction; 3) Target vessel revascularization (TVR). Angiographically confirmed by core lab. |
| Change in TyG Index from Baseline to 90 days | Baseline, 90 days | Triglyceride-glucose index calculated as ln\[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2\]. |
| SAQ-7 Angina Frequency Score at baseline, 3, 6, 12 Months | Baseline, 3, 6, 12 Months | Seattle Angina Questionnaire (SAQ-7) Domain 1 (Angina Frequency). Scale: 0-100 (higher=better). |
| EQ-5D-5L Utility Score at baseline, 3, 6, 12 Months | Baseline, 3, 6, 12 Months | EuroQol 5-Dimension 5-Level (EQ-5D-5L) health-related quality of life. Scale: 0-1 (higher=better). |
| Heart Failure Readmission Rate at 180 Days and 365 Days | 180 days, 365 days | Proportion of participants hospitalized for worsening heart failure (per modified Framingham criteria) within 180 days and 365 days post-treatment. Adjudicated by blinded Clinical Events Committee. |
| 30-day Severe STEMI Complications (Killip Class II-IV) | 30 days | Composite of: 1) Cardiogenic shock (Killip IV); 2) Acute heart failure (Killip II-III); 3) Mechanical complications (e.g., ventricular septal rupture); 4) Malignant arrhythmia (sustained VT/VF). Assessed by adjudication committee. |
| 30-day Severe Bleeding (BARC Type 3 or 5) | 30 days | Bleeding Academic Research Consortium (BARC) criteria: Type 3 (overt bleeding with hemoglobin drop ≥3 g/dL or transfusion) or Type 5 (fatal bleeding). |
| Change in LVEF (%) from Baseline to 90 days | Baseline, 90 days | Left ventricular ejection fraction measured by echocardiography (Simpson's biplane method). |
Other
| Measure | Time frame | Description |
|---|---|---|
| 12-month Renal Composite Endpoint | 12 months | Composite of: 1) Sustained ≥50% decline in eGFR from baseline; 2) Sustained eGFR \<15 mL/min/1.73 m²; 3) Initiation of long-term dialysis or renal transplantation. |
| Change in Tubular Markers (α1-MG, β2-MG, NAG) at 12 Months | Baseline, 12 months | Urinary biomarkers of tubular injury: α1-microglobulin (α1-MG), β2-microglobulin (β2-MG), and N-acetyl-β-D-glucosaminidase (NAG). Concentrations measured by immunoturbidimetry (α1-MG, β2-MG) and enzymatic assay (NAG). |
| Rate of Change in eGFR (mL/min/1.73 m²/year) | Baseline, 6 months, 12 months | Estimated glomerular filtration rate (eGFR) calculated using CKD-EPI formula. Annualized rate of change derived from serial measurements at baseline, 6, and 12 months. |
| Rate of Change in UACR (mg/g/year) | Baseline, 6 months, 12 months | Urine albumin-to-creatinine ratio (UACR) measured from first-morning void samples. Annualized rate of change calculated from baseline, 6, and 12-month data. |
Countries
China
Contacts
Primary ContactTao Huang
Backup ContactZheng Zhen
Outcome results
None listed