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Trial record 9 of 509 for:    ASPIRIN AND P2

Anti-platelet Effect of Berberine in Patients After Elective Percutaneous Coronary Intervention (APLABE-PCI)

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ClinicalTrials.gov Identifier: NCT03378934
Recruitment Status : Recruiting
First Posted : December 20, 2017
Last Update Posted : October 3, 2018
Sponsor:
Information provided by (Responsible Party):
LiuZhenyu, Peking Union Medical College Hospital

Tracking Information
First Submitted Date  ICMJE December 14, 2017
First Posted Date  ICMJE December 20, 2017
Last Update Posted Date October 3, 2018
Actual Study Start Date  ICMJE September 26, 2018
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 1, 2018)
P2Y12 reaction unit (PRU) [ Time Frame: On the 12th (11th-13th) week of treatment ]
The P2Y12 reaction unit (PRU) assessed by VerifyNow assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of the treatment period (Visit 4, EOT), i.e., on the 12th (11th-13th) week of treatment
Original Primary Outcome Measures  ICMJE
 (submitted: December 14, 2017)
P2Y12 reaction unit (PRU) [ Time Frame: At the 12th (11th-13th) week of treatment ]
The P2Y12 reaction unit (PRU) assessed by VerifyNow assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of the treatment period (Visit 4, EOT), i.e., the 12th (11th-13th) week of treatment
Change History Complete list of historical versions of study NCT03378934 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 1, 2018)
  • P2Y12 reaction unit (PRU) [ Time Frame: On the 8th (7th-9th) week of treatment ]
    The P2Y12 reaction unit (PRU) assessed by VerifyNow assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 2 (Visit 3) [ i.e., on the 8th (7th-9th) week of treatment ]
  • P2Y12 reaction unit (PRU) [ Time Frame: On the 4th (3rd-5th) week of treatment ]
    The P2Y12 reaction unit (PRU) assessed by VerifyNow assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 1 (Visit 2) [ i.e., on the 4th (3rd-5th) week of treatment ]
  • Platelet reactivity index (PRI) [ Time Frame: On the 12th (11th-13th) week of treatment ]
    The platelet reactivity index (PRI) assessed by vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of the treatment period (Visit 4, EOT) [ i.e., on the 12th (11th-13th) week of treatment ]
  • Platelet reactivity index (PRI) [ Time Frame: On the 8th (7th-9th) week of treatment ]
    The platelet reactivity index (PRI) assessed by vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 2 (Visit 3) [ i.e., on the 8th (7th-9th) week of treatment ]
  • Platelet reactivity index (PRI) [ Time Frame: On the 4th (3rd-5th) week of treatment ]
    The platelet reactivity index (PRI) assessed by vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 1 (Visit 2) [ i.e., on the 4th (3rd-5th) week of treatment ]
  • Urinary 11-dehydro-thromboxane B2 (11-dH-TXB2) [ Time Frame: On the 12th (11th-13th) week of treatment ]
    The urinary 11-dehydro-thromboxane B2 (11-dH-TXB2) assessed by enzyme-linked immunosorbent assay (ELISA) 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of the treatment period (Visit 4, EOT) [ i.e., on the 12th (11th-13th) week of treatment ]
  • Urinary 11-dehydro-thromboxane B2 (11-dH-TXB2) [ Time Frame: On the 8th (7th-9th) week of treatment ]
    The urinary 11-dehydro-thromboxane B2 (11-dH-TXB2) assessed by enzyme-linked immunosorbent assay (ELISA) 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 2 (Visit 3) [ i.e., on the 8th (7th-9th) week of treatment ]
  • Urinary 11-dehydro-thromboxane B2 (11-dH-TXB2) [ Time Frame: On the 4th (3rd-5th) week of treatment ]
    The urinary 11-dehydro-thromboxane B2 (11-dH-TXB2) assessed by enzyme-linked immunosorbent assay (ELISA) 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 1 (Visit 2) [ i.e., on the 4th (3rd-5th) week of treatment ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 14, 2017)
  • P2Y12 reaction unit (PRU) [ Time Frame: At the 8th (7th-9th) week of treatment ]
    The P2Y12 reaction unit (PRU) assessed by VerifyNow assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 2 (Visit 3) [ i.e., the 8th (7th-9th) week of treatment ]
  • P2Y12 reaction unit (PRU) [ Time Frame: At the 4th (3rd-5th) week of treatment ]
    The P2Y12 reaction unit (PRU) assessed by VerifyNow assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 1 (Visit 2) [ i.e., the 4th (3rd-5th) week of treatment ]
  • Aspirin reaction unit (ARU) [ Time Frame: At the 12th (11th-13th) week of treatment ]
    The aspirin reaction unit (ARU) assessed by VerifyNow assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of the treatment period (Visit 4, EOT) [ i.e., the 12th (11th-13th) week of treatment ]
  • Aspirin reaction unit (ARU) [ Time Frame: At the 8th (7th-9th) week of treatment ]
    The aspirin reaction unit (ARU) assessed by VerifyNow assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 2 (Visit 3) [ i.e., the 8th (7th-9th) week of treatment ]
  • Aspirin reaction unit (ARU) [ Time Frame: At the 4th (3rd-5th) week of treatment ]
    The aspirin reaction unit (ARU) assessed by VerifyNow assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 1 (Visit 2) [ i.e., the 4th (3rd-5th) week of treatment ]
  • Platelet reactivity index (PRI) [ Time Frame: At the 12th (11th-13th) week of treatment ]
    The platelet reactivity index (PRI) assessed by vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of the treatment period (Visit 4, EOT) [ i.e., the 12th (11th-13th) week of treatment ]
  • Platelet reactivity index (PRI) [ Time Frame: At the 8th (7th-9th) week of treatment ]
    The platelet reactivity index (PRI) assessed by vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 2 (Visit 3) [ i.e., the 8th (7th-9th) week of treatment ]
  • Platelet reactivity index (PRI) [ Time Frame: At the 4th (3rd-5th) week of treatment ]
    The platelet reactivity index (PRI) assessed by vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 1 (Visit 2) [ i.e., the 4th (3rd-5th) week of treatment ]
  • Urinary 11-dehydro-thromboxane B2 (11-dH-TXB2) [ Time Frame: At the 12th (11th-13th) week of treatment ]
    The urinary 11-dehydro-thromboxane B2 (11-dH-TXB2) assessed by enzyme-linked immunosorbent assay (ELISA) 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of the treatment period (Visit 4, EOT) [ i.e., the 12th (11th-13th) week of treatment ]
  • Urinary 11-dehydro-thromboxane B2 (11-dH-TXB2) [ Time Frame: At the 8th (7th-9th) week of treatment ]
    The urinary 11-dehydro-thromboxane B2 (11-dH-TXB2) assessed by enzyme-linked immunosorbent assay (ELISA) 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 2 (Visit 3) [ i.e., the 8th (7th-9th) week of treatment ]
  • Urinary 11-dehydro-thromboxane B2 (11-dH-TXB2) [ Time Frame: At the 4th (3rd-5th) week of treatment ]
    The urinary 11-dehydro-thromboxane B2 (11-dH-TXB2) assessed by enzyme-linked immunosorbent assay (ELISA) 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 1 (Visit 2) [ i.e., the 4th (3rd-5th) week of treatment ]
  • P-selectin (CD62p) expression [ Time Frame: At the 12th (11th-13th) week of treatment ]
    The P-selectin (CD62p) expression assessed by flow cytometry 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of the treatment period (Visit 4, EOT) [ i.e., the 12th (11th-13th) week of treatment ]
  • P-selectin (CD62p) expression [ Time Frame: At the 8th (7th-9th) week of treatment ]
    The P-selectin (CD62p) expression assessed by flow cytometry 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 2 (Visit 3) [ i.e., the 8th (7th-9th) week of treatment ]
  • P-selectin (CD62p) expression [ Time Frame: At the 4th (3rd-5th) week of treatment ]
    The P-selectin (CD62p) expression assessed by flow cytometry 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of Stage 1 (Visit 2) [ i.e., the 4th (3rd-5th) week of treatment ]
Current Other Pre-specified Outcome Measures
 (submitted: October 1, 2018)
  • Major adverse cardiac events (MACE) [ Time Frame: Up to the 12th (11th-13th) week of treatment ]
    The composite of death, or myocardial infarction, or urgent coronary revascularization, or definite or possible stent thrombosis, up to the end of the treatment period (Visit 4, EOT), i.e., the 12th (11th-13th) week of treatment
  • Major bleeding [ Time Frame: Up to the 12th (11th-13th) week of treatment ]
    The major bleeding according to platelet inhibition and patient outcomes (PLATO) definition up to the end of the treatment period (Visit 4, EOT), i.e., the 12th (11th-13th) week of treatment
  • Minor bleeding [ Time Frame: Up to the 12th (11th-13th) week of treatment ]
    The minor bleeding according to platelet inhibition and patient outcomes (PLATO) definition up to the end of the treatment period (Visit 4, EOT), i.e., the 12th (11th-13th) week of treatment
  • Minimal bleeding [ Time Frame: Up to the 12th (11th-13th) week of treatment ]
    The minimal bleeding according to platelet inhibition and patient outcomes (PLATO) definition up to the end of the treatment period (Visit 4, EOT), i.e., the 12th (11th-13th) week of treatment
  • Major or minor bleeding [ Time Frame: Up to the 12th (11th-13th) week of treatment ]
    The major or minor bleeding according to platelet inhibition and patient outcomes (PLATO) definition up to the end of the treatment period (Visit 4, EOT), i.e., the 12th (11th-13th) week of treatment
  • Major or minor or minimal bleeding [ Time Frame: Up to the 12th (11th-13th) week of treatment ]
    The major or minor or minimal bleeding according to platelet inhibition and patient outcomes (PLATO) definition up to the end of the treatment period (Visit 4, EOT), i.e., the 12th (11th-13th) week of treatment
  • P-selectin (CD62p) expression [ Time Frame: On the 12th (11th-13th) week of treatment ]
    The P-selectin (CD62p) expression assessed by flow cytometry 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of the treatment period (Visit 4, EOT) [ i.e., the 12th (11th-13th) week of treatment ]
  • Serum soluble P-selectin (sCD62p) [ Time Frame: On the 12th (11th-13th) week of treatment ]
    Serum soluble P-selectin (sCD62p) assessed by enzyme-linked immunosorbent assay (ELISA) 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of the treatment period (Visit 4, EOT) [ i.e., on the 12th (11th-13th) week of treatment ]
  • Serum soluble CD40 ligand (sCD40L) [ Time Frame: On the 12th (11th-13th) week of treatment ]
    Serum soluble CD40 ligand (sCD40L) assessed by enzyme-linked immunosorbent assay (ELISA) 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of the treatment period (Visit 4, EOT) [ i.e., on the 12th (11th-13th) week of treatment ]
Original Other Pre-specified Outcome Measures
 (submitted: December 14, 2017)
  • Major adverse cardiac events (MACE) [ Time Frame: Up to the 12th (11th-13th) week of treatment ]
    The composite of death, or myocardial infarction, or urgent coronary revascularization, or definite or possible stent thrombosis, up to the end of the treatment period (Visit 4, EOT), i.e., the 12th (11th-13th) week of treatment
  • Major bleeding [ Time Frame: Up to the 12th (11th-13th) week of treatment ]
    The major bleeding according to platelet inhibition and patient outcomes (PLATO) definition up to the end of the treatment period (Visit 4, EOT), i.e., the 12th (11th-13th) week of treatment
  • Minor bleeding [ Time Frame: Up to the 12th (11th-13th) week of treatment ]
    The minor bleeding according to platelet inhibition and patient outcomes (PLATO) definition up to the end of the treatment period (Visit 4, EOT), i.e., the 12th (11th-13th) week of treatment
  • Minimal bleeding [ Time Frame: Up to the 12th (11th-13th) week of treatment ]
    The minimal bleeding according to platelet inhibition and patient outcomes (PLATO) definition up to the end of the treatment period (Visit 4, EOT), i.e., the 12th (11th-13th) week of treatment
  • Major or minor bleeding [ Time Frame: Up to the 12th (11th-13th) week of treatment ]
    The major or minor bleeding according to platelet inhibition and patient outcomes (PLATO) definition up to the end of the treatment period (Visit 4, EOT), i.e., the 12th (11th-13th) week of treatment
  • Major or minor or minimal bleeding [ Time Frame: Up to the 12th (11th-13th) week of treatment ]
    The major or minor or minimal bleeding according to platelet inhibition and patient outcomes (PLATO) definition up to the end of the treatment period (Visit 4, EOT), i.e., the 12th (11th-13th) week of treatment
 
Descriptive Information
Brief Title  ICMJE Anti-platelet Effect of Berberine in Patients After Elective Percutaneous Coronary Intervention
Official Title  ICMJE A Single-center, Randomized, Open-label, Controlled, Dose-escalating, Parallel-group Study to Assess the Anti-platelet Effect of Berberine in Patients Receiving Aspirin and Clopidogrel After Elective Percutaneous Coronary Intervention for Stable Coronary Artery Disease or Unstable Angina
Brief Summary The APLABE-PCI is a single-center, randomized, open-label, controlled, dose-escalating, parallel-group study, which is designed to assess the anti-platelet effect of berberine in approximately 64 patients receiving aspirin and clopidogrel who are at > 8 but ≤ 40 weeks after elective percutaneous coronary intervention for stable coronary artery disease or unstable angina.
Detailed Description

Background

Dual antiplatelet therapy (DAPT) with aspirin and a platelet P2Y12 inhibitor is mandatory in patients after percutaneous coronary intervention (PCI). For patients with stable coronary artery disease (SCAD) and unstable angina (UA), clopidogrel is the most widely used P2Y12 inhibitor with class I recommendation. However, clopidogrel is a pro-drug which has highly variable antiplatelet effect. Hypo-responsiveness to clopidogrel was associated with increased risk of thrombotic events after PCI.

Increasing the dose of aspirin could not reduce thrombotic risk but resulted in elevated bleeding risk. Although new P2Y12 inhibitors have more potent antiplatelet effect and did reduce thrombotic risk compared with clopidogrel, the benefit was only demonstrated in patients undergoing PCI for moderate to high risk non-ST-segment elevation acute coronary syndrome (NSTE-ACS) or ST-segment elevation myocardial infarction (STEMI) and was also associated with increased bleeding risk. Therefore, how to improve the antiplatelet therapy in patients taking aspirin and clopidogrel after elective PCI for SCAD or UA remains unclear.

Berberine is an isoquinoline plant alkaloid which has anti-inflammatory, anti-oxidant, anti-microbial, anti-tumoral and immunomodulatory properties, as well as anti-hypertensive, hypo-glycemic and cholesterol-lowering effects. In small studies conducted in patients with hypertension, hypercholesterolemia and diabetes, berberine with a daily dose of 600-1000 mg for 12 weeks had good safety profile and was well tolerated.

In addition, berberine demonstrated antiplatelet effect. After in vivo administration in animals, berberine inhibited ex vivo platelet activation mediated by P2Y12 receptor and ex vivo platelet aggregation induced by adenosine diphosphate (ADP), arachidonic acid (AA), collagen, and thrombin, et al. After ex vivo administration, berberine inhibited ex vivo thromboxane B2 (TXB2) synthesis induced by ADP, AA, and collagen in animal platelets, as well as ex vivo platelet aggregation induced by collagen in a dose-dependent manner in platelets from healthy human volunteers. However, the antiplatelet effect of berberine has never been investigated in patients receiving DAPT after PCI.

Design

The APLABE-PCI is a single-center, randomized, open-label, controlled, dose-escalating, parallel-group study, which is designed to assess the anti-platelet effect of berberine in approximately 64 patients receiving aspirin and clopidogrel who are at > 8 but ≤ 40 weeks after elective PCI for SCAD or UA.

The total study duration is expected to be approximately 19 weeks per patient, including a screening period, a 12±1 week treatment period, and a 4±1 week follow-up period.

The visit schedule will be as follows:

  • Visit 0 (V0): Day -21 to Day -1, Screening/Enrolment;
  • Visit 1 (V1): Day 1, Randomization/First dose;
  • Visit 2 (V2): Week 4±1, Dose adjustment 1;
  • Visit 3 (V3): Week 8±1, Dose adjustment 2;
  • Visit 4 (V4): Week 12±1, End of Treatment (EOT) /Last dose; •Visit 5 (V5): Week 16±1, Safety visit.

The screening period will be up to 21 days. Once each patient has signed the informed consent, the eligibility of the patient will be evaluated and related laboratory assessments will be taken (Visit 0). All patients will continue taking aspirin and clopidogrel in the morning during the screening period.

On the first day of the treatment period (Visit 1), eligible patients will return to the study center and be randomized into the Berberine Arm and the Control Arm. In the Berberine Arm, patients will receive berberine 200 mg twice daily for 4±1 weeks (Stage 1); then, 300 mg twice daily for 4±1 weeks (Stage 2); then, 400 mg twice daily for 4±1 weeks (Stage 3) in addition to standard treatment, including aspirin and clopidogrel. In the Control Arm, patients will receive standard treatment, including aspirin and clopidogrel, for 12±1 weeks. During the treatment period, patients in both arms will also take aspirin 100 mg once daily and clopidogrel 75 mg once daily for 12±1 weeks.

The total daily dose of berberine will be taken separately in the morning and in the evening in approximately a 12-hour interval. On the first day of the treatment period (Visit 1), the morning dose (first dose) of berberine will be given 2-4 hour after aspirin and clopidogrel are taken in the morning and immediately after the blood and urine samples for baseline platelet function tests are collected. Since the second day of the treatment period, the morning dose of berberine will be taken simultaneously with aspirin and clopidogrel in the morning.

At the ends of Stage 1 (Visit 2), Stage 2 (Visit 3), and Stage 3 (Visit 4) (end of treatment, EOT), patients will return to the study center. During each stage, the last morning doses of all antiplatelet agents, including berberine, aspirin, and clopidogrel in the Berberine Arm, as well as aspirin and clopidogrel in the Control Arm, will be administered simultaneously at the study center in the morning on Visit 2, Visit 3, and Visit 4, respectively.

A follow-up period will begin on the next day after Visit 4 and will continue for 4±1 weeks. During the follow-up period, patients in both arms will continue taking aspirin and clopidogrel. At the end of the follow-up period, patients will return to the study center for a safety visit (Visit 5).

In the Berberine Arm, the blood and urine samples for platelet function tests will be obtained 2-4 hour after aspirin and clopidogrel are taken in the morning and before the first morning dose of berberine is taken on Visit 1, and 2-4 hours after the morning doses of berberine, aspirin and clopidogrel are taken on Visit 2, Visit 3, and Visit 4, respectively. In the Control Arm, the blood and urine samples for platelet function tests will be collected 2-4 hours after the morning doses of aspirin and clopidogrel are given on Visit 1, Visit 2, Visit 3, and Visit 4, respectively.

In the Berberine Arm, the blood and urine samples for safety assessment will be collected on Visit 0, and 2-4 hours after the morning doses of berberine, aspirin and clopidogrel are taken on Visit 2, Visit 3, and Visit 4, as well as on Visit 5, respectively. In the Control Arm, the blood and urine samples for safety assessment will be collected on Visit 0, and 2-4 hours after the morning doses of aspirin and clopidogrel are taken on Visit 2, Visit 3, and Visit 4, as well as on Visit 5, respectively.

Adverse events will be collected on Visit 1, Visit 2, Visit 3, Visit 4, and Visit 5, respectively. Cardiac ischemic events and bleeding events will be collected on Visit 2, Visit 3, and Visit 4, respectively.

The primary endpoint of the study is P2Y12 reaction unit (PRU) assessed by VerifyNow assay 2-4 h after all the antiplatelet agents are taken simultaneously in the morning at the end of the treatment period (Visit 4, EOT), i.e., on the 12th (11th-13th) week of treatment.

Conclusions

The APLABE-PCI study will assess the anti-platelet effect of berberine in patients receiving aspirin and clopidogrel after elective PCI for SCAD or UA. The result of the present study would provide pharmacodynamical data for the design of future outcome studies.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

On the first day of the treatment period (Visit 1), eligible patients will be randomized into the Berberine Arm and the Control Arm.

In the Berberine Arm, patients will receive berberine 200 mg twice daily for 4±1 weeks (Stage 1); then, 300 mg twice daily for 4±1 weeks (Stage 2); then, 400 mg twice daily for 4±1 weeks (Stage 3) in addition to standard treatment, including aspirin 100 mg once daily and clopidogrel 75 mg once daily for 12±1 weeks.

In the Control Arm, patients will receive standard treatment, including aspirin 100 mg once daily and clopidogrel 75 mg once daily for 12±1 weeks.

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Coronary Artery Disease
  • Percutaneous Coronary Intervention
Intervention  ICMJE
  • Drug: Berberine
    Berberine 200 mg twice daily for 4±1 weeks (Stage 1); then, 300 mg twice daily for 4±1 weeks (Stage 2); then, 400 mg twice daily for 4 weeks (Stage 3).
    Other Name: Berberine Hydrochloride Tablets
  • Drug: Standard treatment
    Standard treatment for 12±1 weeks.
  • Drug: Aspirin
    Aspirin 100 mg once daily for 12±1 weeks.
    Other Names:
    • Aspirin Enteric-coated Tablets
    • Bayaspirin
  • Drug: Clopidogrel
    Clopidogrel 75 mg once daily for 12±1 weeks.
    Other Names:
    • Clopidogrel Hydrogen Sulphate Tablets
    • Plavix
Study Arms  ICMJE
  • Experimental: Berberine Arm
    In the Berberine Arm, patients will receive berberine 200 mg twice daily for 4±1 weeks (Stage 1); then, 300 mg twice daily for 4±1 weeks (Stage 2); then, 400 mg twice daily for 4±1 weeks (Stage 3) in addition to standard treatment, including aspirin 100 mg once daily and clopidogrel 75 mg once daily for 12±1 weeks.
    Interventions:
    • Drug: Berberine
    • Drug: Standard treatment
    • Drug: Aspirin
    • Drug: Clopidogrel
  • Active Comparator: Control Arm
    In the Control Arm, patients will receive standard treatment, including aspirin 100 mg once daily and clopidogrel 75 mg once daily for 12±1 weeks.
    Interventions:
    • Drug: Standard treatment
    • Drug: Aspirin
    • Drug: Clopidogrel
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 14, 2017)
64
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2020
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria

  1. Provision of written informed consent.
  2. Aged 18-70 years, male or female.
  3. Currently, > 8 but ≤ 40 weeks after elective percutaneous coronary intervention (PCI) for stable coronary disease (SCAD) or unstable angina (UA).
  4. Receiving dual antiplatelet therapy (DAPT) with aspirin (Bayaspirin TM) 100 mg once daily and clopidogrel (Plavix TM) 75 mg once daily for ≥ 7 days.
  5. No cardiac ischemic events or bleeding events occurred after the index PCI.

    • Cardiac ischemic events include myocardial infarction, coronary revascularization, and definite or probable stent thrombosis;
    • Bleeding events include major or minor bleeding according to the Platelet Inhibition and Patient Outcomes (PLATO) definition.
  6. PRECISE-DAPT score < 25 evaluated after the index PCI and before the index hospital discharge.
  7. Females who are either post-menopausal > 1 year or surgically sterile.

Exclusion criteria

  1. The indication of the index PCI was acute myocardial infarction, including ST-segment elevation myocardial infarction or non-ST-segment elevation myocardial infarction.
  2. Use of any fibrinolytic or antithrombotic agents, with the exception of aspirin and clopidogrel within 30 day of screening.
  3. Any indications other than coronary artery disease (e.g., atrial fibrillation, prosthetic heart valve, venous thromboembolism, ventricular thrombosis, et al) for fibrinolytic or antithrombotic treatment during the study period.
  4. Planned use of any fibrinolytic or antithrombotic agents, with the exception of aspirin (Bayaspirin TM) and clopidogrel (Plavix TM) during the study period.
  5. Planned use of moderate or strong cytochrome P450 (CYP) 2C19 inhibitors, CYP2C19 substrates with narrow therapeutic index, or strong CYP2C19 inducers during the study period.
  6. Planned coronary revascularization, including PCI and coronary artery bypass graft (CABG) during the study period.
  7. Increased bleeding risk, including

    • any history of intracranial, intraocular, retroperitoneal, or spinal bleeding;
    • recent (within 30 days of screening) gastrointestinal (GI) bleeding;
    • recent (within 30 days of screening) major trauma or major surgery;
    • planned surgery or other invasive procedure during the study period;
    • sustained uncontrolled hypertension (systolic blood pressure [SBP] > 180 mmHg or diastolic blood pressure [DBP] > 100 mmHg);
    • history of hemorrhagic disorders, e.g., haemophilia, von Willebrand's disease;
    • inability to discontinue non-steroidal anti-inflammatory drugs (NSAIDs) during the study period;
    • platelet count less than 100,000/mm3 or hemoglobin < 10 g/dL.
  8. Contraindications for aspirin, clopidogrel, and berberine, e.g., hypersensitivity, active bleeding, bleeding diathesis, coagulation disorders, severe liver or kidney diseases, hemolytic anemia, glucose-6-phosphate dehydrogenase deficiency, et al.
  9. History of intolerance to aspirin, clopidogrel, and berberine.
  10. Any condition, which in the opinion of the Investigator, would make it unsuitable for the patient to participate in this study. For example, conditions which may put the patient at risk, e.g., liver or kidney dysfunction, et al; or increase the risk of non-compliance to study protocol or follow-up, e.g., history of drug addiction or alcohol abuse, et al; or influence the result of the study, e.g., active cancer, et al.
  11. Patients who has previously been randomized in this study.
  12. Participation in another investigational drug or device study within 30 days of screening.
  13. Involvement in the planning and conduct of the study (applies to investigators, contract research organization staff, and study site staff, et al).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Zhenyu Liu, M.D. +861069155068 pumch_lzy@163.com
Contact: Lihong Xu, B.N. +861069155068 xulihong1990@163.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03378934
Other Study ID Numbers  ICMJE 2016-I2M-1-011
JS-1375 ( Other Identifier: Ethics Committee in Peking Union Medical College Hospital )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party LiuZhenyu, Peking Union Medical College Hospital
Study Sponsor  ICMJE Peking Union Medical College Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Zhenyu Liu, M.D. Department of Cardiology, Peking Union Medical College Hospital
PRS Account Peking Union Medical College Hospital
Verification Date October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP