Effects of Dengzhanxixin Capsule on Platelet Function in Individuals at High Risk for Cardiovascular Disease

Study Overview
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Brief Summary
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The main objective of this clinical trial is to evaluate whether the antiplatelet efficacy of the Dengzhanxixin capsule is better than that of placebo in individuals at high-risk for atherosclerotic cardiovascular disease (ASCVD).

Detailed Description
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Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of cardiovascular death, and one out of every ten people aged 35-75 in China is at high risk for ASCVD. Platelet activation is an important mechanism for the development of atherosclerosis. Antiplatelet therapy is important in preventing ASCVD. Dengzhanxixin capsule is an over-the-counter Chinese traditional medicine; currently, it is mainly used for the adjuvant treatment of ischemic stroke and coronary heart disease. A study of 3143 patients with ischemic stroke found that the addition of Dengzhanshengmai capsules to the standard treatment could further reduce the risk of recurrent stroke and was well tolerated without increased risk of bleeding. Animal experiments also observed that Dengzhanxixin capsules had a clear antiplatelet effect. However, the antiplatelet function of Dengzhanxixin capsules in humans is still unclear. In addition, Dengzhanxixin capsules also have potential anti-inflammatory, lipid-lowering, anticoagulant, and antihypertensive effects. The main objective of this study is to evaluate the antiplatelet efficacy and safety of Dengzhanxixin capsules in individuals at high-risk for ASCVD. The plan of the study is to recruit 165 subjects and the follow up is to be 10 weeks. This study has been approved by the Ethics Committee of Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen.

Official Title
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Effects of Dengzhanxixin Capsule on Platelet Function in Individuals at High Risk for Cardiovascular Disease (FUTURE): a Multi-center, Double-blinded, Randomized, Placebo-controlled Trial

Conditions
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Diabetes, Hypertension, Hypercholesterolemia

Intervention / Treatment
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* Drug: Dengzhanxixin Capsule plus Placebo Capsule
* Drug: Placebo
* Drug: Dengzhanxixin Capsule plus Placebo Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The following three conditions must be met at the same time: Age > 40 years, < 70 years Meet any of the following conditions: i) Diabetes ii) LDL-C ≥ 4.9 mmol/L or TC ≥ 7.2 mmol/L iii) Hypertension; 1.8 mmol/L ≤ LDL-C < 2.6 mmol/L or 3.1 mmol/L ≤ TC < 4.1 mmol/L; 3 risk factors (including smoking, HDL-C < 1.0 mmol/L, ≥ 45 years for male or ≥ 55 years for female) iv) Hypertension; 2.6mmol/L ≤ LDL-C < 4.9mmol/L or 4.1mmol/L ≤ TC < 7.2mmol/L; with 2 or more risk factors (same risk factors as above) Sign the informed consent Exclusion Criteria: Those who meet any of the following conditions are not eligible: Diagnosed ASCVD, such as coronary heart disease, stroke and peripheral vascular disease Past history of heart failure History of symptomatic non-traumatic intracerebral hemorrhage at any time History of gastrointestinal bleeding within the past 3 months or history of major surgery within 30 days Need to use anticoagulation, antiplatelet or frequent use of non-steroidal anti-inflammatory drugs Have used Dengzhanxixin or preparations containing Dengzhanxixin in the past 1 month Have clear adverse reactions to Dengzhanxixin in the past Active liver disease, or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 2 times the upper limit of normal (ULN) Chronic kidney disease, or estimated glomerular filtration rate (eGFR) <60ml/(min×1.73m2) Pregnant or planning to become pregnant, or breastfeeding Malignant tumors, or other serious diseases with an expected survival period of less than 1 year Mental disorders or communication disorders, cognitive dysfunction, or other serious diseases that may affect participation in the study Have participated in or are participating in other clinical trials in the past 1 month Known poor adherence to study follow-up or study medication Acute stage of disease: acute fever, acute pancreatitis, etc. In addition, subjects will be excluded from the randomization clinic if they have any of the following situations: Failure to complete the lead-in treatment The occurrence of placebo-related adverse reactions

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group A<br>Dengzhanxixin Capsules plus Placebo Capsules | Drug: Dengzhanxixin Capsule plus Placebo Capsule<br>* Dengzhanxixin Capsule, 0.54g (3 capsules) each time, twice daily; placebo, 1 capsule, twice daily<br>|
| Experimental: Intervention group B<br>Dengzhanxixin Capsules plus Placebo Capsules | Drug: Dengzhanxixin Capsule plus Placebo Capsule<br>* Dengzhanxixin Capsule, 0.72g (4 capsules) each time, once daily; placebo, 4 capsules, once daily<br>|
| Placebo Comparator: Control group<br>Placebo Capsules | Drug: Placebo<br>* Placebo, 4 capsules each time, twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in rate of platelet aggregation | inhibition of adenosine diphosphate (ADP)-induced platelet aggregation as measured by optical aggregometry at week 8. | Day 0, Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in rate of platelet aggregation | inhibition of arachidonic acid (AA) and collagen (COLL) -induced platelet aggregation measured by optical aggregometry at week 8. inhibition of ADP, AA and COLL -induced platelet aggregation measured by optical aggregometry at week 4. At 4 weeks and 8 weeks from baseline, compare the differences of platelet P2Y12 response units (PRU) and aspirin response units (ARU) At 4 weeks and 8 weeks of treatment, compare the differences of P-selectin. | Day 0,Week 4,Week 8 | 
| Changes in blood pressure | Changes in systolic blood pressure (mmHg) and diastolic blood pressure (mmHg) at 4 and 8 weeks of treatment compared with baseline | Day 0,Week 4,Week 8 | 
| Changes in serum lipid profile | changes in total cholesterol (mg/dL) , low-density lipoprotein cholesterol ester (mg/dL) , high-density lipoprotein cholesterol ester (mg/dL) , triglyceride (mg/dL) and lipoprotein(a) (mg/dL) at 4 and 8 weeks of treatment compared with baseline | Day 0,Week 4,Week 8 | 
| Changes in coagulation profile | changes in prothrombin time (s), activated partial thromboplastin time (s), and thrombin time (s) at 4 and 8 weeks of treatment compared with baseline | Day 0,Week 4,Week 8 | 
| Changes in fibrinogen | changes in fibrinogen (g/L) at 4 and 8 weeks of treatment compared with baseline | Day 0,Week 4,Week 8 | 
| Changes in hs-CRP | changes in high-sensitivity C-reactive protein (mg/dL) at 4 and 8 weeks of treatment compared with baseline | Day 0,Week 4,Week 8 | 
| Changes in IL-6 | changes in interleukin-6 (pg/mL) at 4 and 8 weeks of treatment compared with baseline | Day 0,Week 4,Week 8 | 
| Changes in HbA1c(%) | Changes in HbA1c at 8 weeks of treatment compared with baseline | Day 0, Week 8 | 
| Number of Participants with safety endpoint | 2) Liver-relate indicators: ALT ≥ 5 times ULN, or ALT ≥ 3 times ULN + bilirubin ≥ 2 times ULN (3) Kidney-related indicators: a. Serum creatinine increased by ≥50% from baseline, or b. Change in eGFR from baseline (4) Serious adverse events (5) Other adverse events related to the study drug (6) Drug discontinuation due to any reason | through study completion, an average of 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dengzhanxixin capsule; platelet function; primary prevention