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

Not Applicable

Recruiting

• Conditions: Diabetes; Hypertension; Hypercholesterolemia
• Interventions: Drug: Dengzhanxixin Capsule plus Placebo Capsule; Drug: Placebo

• Registration Number: NCT05459519
• Lead Sponsor: China National Center for Cardiovascular Diseases

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2022-06-26
• Study First Submitted QC: 2022-07-12
• Study First Posted: 2022-07-15
• Study Start: 2022-07-20
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-23
• Last Update Posted: 2023-07-25
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 165

Inclusion Criteria

The following three conditions must be met at the same time:

1. Age > 40 years, < 70 years

2. 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)

3. Sign the informed consent

Exclusion Criteria

Those who meet any of the following conditions are not eligible:

1. Diagnosed ASCVD, such as coronary heart disease, stroke and peripheral vascular disease
2. Past history of heart failure
3. History of symptomatic non-traumatic intracerebral hemorrhage at any time
4. History of gastrointestinal bleeding within the past 3 months or history of major surgery within 30 days
5. Need to use anticoagulation, antiplatelet or frequent use of non-steroidal anti-inflammatory drugs
6. Have used Dengzhanxixin or preparations containing Dengzhanxixin in the past 1 month
7. Have clear adverse reactions to Dengzhanxixin in the past
8. Active liver disease, or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 2 times the upper limit of normal (ULN)
9. Chronic kidney disease, or estimated glomerular filtration rate (eGFR) <60ml/(min×1.73m2)
10. Pregnant or planning to become pregnant, or breastfeeding
11. Malignant tumors, or other serious diseases with an expected survival period of less than 1 year
12. Mental disorders or communication disorders, cognitive dysfunction, or other serious diseases that may affect participation in the study
13. Have participated in or are participating in other clinical trials in the past 1 month
14. Known poor adherence to study follow-up or study medication
15. 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:

1. Failure to complete the lead-in treatment
2. The occurrence of placebo-related adverse reactions

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention group A	Dengzhanxixin Capsule plus Placebo Capsule	Dengzhanxixin Capsules plus Placebo Capsules
Intervention group B	Dengzhanxixin Capsule plus Placebo Capsule	Dengzhanxixin Capsules plus Placebo Capsules
Control group	Placebo	Placebo Capsules

Primary Outcome Measures

Name	Time	Method
Changes in rate of platelet aggregation	"Day 0", "Week 8"	inhibition of adenosine diphosphate (ADP)-induced platelet aggregation as measured by optical aggregometry at week 8.

Secondary Outcome Measures

Name	Time	Method
Changes in rate of platelet aggregation	"Day 0","Week 4","Week 8"	1. inhibition of arachidonic acid (AA) and collagen (COLL) -induced platelet aggregation measured by optical aggregometry at week 8.; 2. inhibition of ADP, AA and COLL -induced platelet aggregation measured by optical aggregometry at week 4.; 3. At 4 weeks and 8 weeks from baseline, compare the differences of platelet P2Y12 response units (PRU) and aspirin response units (ARU); 4. At 4 weeks and 8 weeks of treatment, compare the differences of P-selectin.
Changes in HbA1c(%)	"Day 0", "Week 8"	Changes in HbA1c at 8 weeks of treatment compared with baseline
Changes in blood pressure	"Day 0","Week 4","Week 8"	Changes in systolic blood pressure (mmHg) and diastolic blood pressure (mmHg) at 4 and 8 weeks of treatment compared with baseline
Changes in coagulation profile	"Day 0","Week 4","Week 8"	changes in prothrombin time (s), activated partial thromboplastin time (s), and thrombin time (s) at 4 and 8 weeks of treatment compared with baseline
Changes in fibrinogen	"Day 0","Week 4","Week 8"	changes in fibrinogen (g/L) at 4 and 8 weeks of treatment compared with baseline
Changes in hs-CRP	"Day 0","Week 4","Week 8"	changes in high-sensitivity C-reactive protein (mg/dL) at 4 and 8 weeks of treatment compared with baseline
Changes in IL-6	"Day 0","Week 4","Week 8"	changes in interleukin-6 (pg/mL) at 4 and 8 weeks of treatment compared with baseline
Number of Participants with safety endpoint	through study completion, an average of 8 weeks	2) Liver-relate indicators: 1. ALT ≥ 5 times ULN, or; 2. 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
Changes in serum lipid profile	"Day 0","Week 4","Week 8"	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

Trial Locations

Locations (1)

Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen; 🇨🇳 ShenZhen, ShenZhen, China