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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Hypertension; Diabetes; Hypercholesterolemia
• Intervention / Treatment: Drug: Dengzhanxixin Capsule plus Placebo Capsule; Drug: Dengzhanxixin Capsule plus Placebo Capsule; Drug: Placebo

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 Type: Interventional
• Enrollment (Estimated): 165
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xin Zheng, Ph.D; Email: xin.zheng@fwoxford.org
• Study Contact Backup: Name: Xiaofang Yan, M.S; Email: xiaofang.yan@fwoxford.org

Study Locations

• China
  • ShenZhen
    • ShenZhen, ShenZhen, China
      • Recruiting
      • Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen
      • Contact: Xin Zheng

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: China National Center for Cardiovascular Diseases
• Collaborators: Fuwai Hospital, Chinese Academy of Medial Sciences, Shenzhen, Shenzhen
• Investigators: Principal Investigator: Xin Zheng, Ph.D, Chinese Academy of Medical Sciences, Fuwai Hospital; Principal Investigator: Jing Li, Ph.D, Chinese Academy of Medical Sciences, Fuwai Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2022
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: June 26, 2022
• First Submitted That Met QC Criteria: July 12, 2022
• First Posted (Actual): July 15, 2022

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 23, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: dengzhanxixin capsule; platelet function; primary prevention
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Cardiovascular Diseases; Hypercholesterolemia
• Other Study ID Numbers: SFLX2022004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No