Comparative Effectiveness Study of Traditional Chinese Medicine Intervention in Ischemic Cerebrovascular Disease Comorbid With Diabetes Mellitus

The population with ischemic cerebrovascular disease (ICVD) comorbid with diabetes is growing, characterized by high mortality, disability, and recurrence rates of vascular events, with a lack of effective treatments. There are 529 million diabetic patients worldwide and 129 million in China, among which 43 million have comorbid vascular diseases; China has approximately 10 million ischemic stroke patients, with 4.5 million comorbid diabetes. Diabetes increases the risk of ischemic stroke, and the proportion of deaths related to diabetic cerebrovascular diseases has risen significantly. Polypharmacy also raises the risk of adverse drug interactions, imposing a heavy medical burden.

The pathological mechanism aligns with the TCM theory of "toxin damaging collaterals": Diabetes-induced glucose/lipid metabolism disorders and activation of the renin-angiotensin-aldosterone system cause systemic vascular endothelial dysfunction and atherosclerosis. Macrovascular lesions mainly involve atherosclerosis, while microvascular lesions include endothelial damage and microcirculatory disorders, with core mechanisms involving energy metabolism abnormalities and mitochondrial dysfunction. TCM holds that "excessive pathogens transform into toxins," and toxin-induced collateral damage disrupts structure and function, consistent with the above pathology. Thus, "detoxification and collaterals dredging" (combining qi-nourishing, blood-activating, and stasis-removing) is the core therapeutic principle.

Chuanzhi Tongluo Capsules (Lunan Pharmaceutical), a Shandong famous brand with annual sales over 100 million yuan, exert effects of promoting blood circulation and dredging collaterals, reducing inflammation and improving microcirculation. This project explores a TCM program combining "acute-phase intensive treatment + recovery-phase sequential treatment" and "universal + syndrome-specific treatment." Entitled Comparative Efficacy Study of TCM Intervention in ICVD Comorbid with Diabetes, this Phase IV trial spans 4 years, adopting a multi-center real-world non-randomized controlled design. It will enroll 3,666 patients with acute cerebral infarction (onset <48h) comorbid diabetes across 50 centers. The control group receives standard secondary prevention of cerebrovascular disease and hypoglycemic treatment; the trial group adds Chuanzhi Tongluo Capsules (4 capsules thrice daily for 14 days, then 2 capsules thrice daily for 1 year) plus syndrome-specific treatment (5 TCM syndromes with corresponding herbs for 14 days).

Inclusion criteria: ≥18 years old, meeting diabetes/acute ischemic stroke criteria, and TCM "toxin damaging brain collaterals" syndrome. Exclusions: hemorrhagic transformation, large infarction, type 1 diabetes, etc. The primary endpoint is the proportion of patients with mRS 0-2 at 90 days. Secondary endpoints include 1-year BARC type III/V major bleeding, MACCE, all-cause mortality, diabetic microvascular lesions (renal indices), mRS, MMSE, and EQ-5D-5L at 6/12 months. Data are managed via EpiData and analyzed with SAS, using chi-square test, t-test, and rank sum test, with 90% statistical power (α=0.05, β=0.10). The trial aims to establish a "disease-syndrome combined" long-term intervention model, expanding TCM applicability and evidence generalization.

English Abbreviation The population with ischemic cerebrovascular disease (ICVD) comorbid with diabetes is growing, with high mortality, disability, and recurrence rates of vascular events, and a lack of effective treatments. Globally, there are 529 million diabetic patients, including 129 million in China, among whom 43 million have comorbid vascular diseases; China has ~10 million ischemic stroke patients, with ~4.5 million comorbid diabetes. Diabetes elevates ischemic stroke risk, and related deaths are increasing, while polypharmacy raises adverse interactions and medical burdens.