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Trial record 79 of 401 for:    ASPIRIN AND clopidogrel AND Purinergic Antagonists

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

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.

Condition or disease Intervention/treatment Phase
Coronary Artery Disease Percutaneous Coronary Intervention Drug: Berberine Drug: Standard treatment Drug: Aspirin Drug: Clopidogrel Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
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
Official Title: 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
Actual Study Start Date : September 26, 2018
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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

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.
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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 ]

  2. 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 ]

  3. 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 ]

  4. 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 ]

  5. 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 ]

  6. 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 ]

  7. 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 ]

  8. 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 ]


Other Outcome Measures:
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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 ]

  8. 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 ]

  9. 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 ]



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03378934


Contacts
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Contact: Zhenyu Liu, M.D. +861069155068 pumch_lzy@163.com
Contact: Lihong Xu, B.N. +861069155068 xulihong1990@163.com

Locations
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China, Beijing
Peking Union Medical College Hospital Recruiting
Beijing, Beijing, China, 100730
Contact: Zhenyu Liu, M.D.    +861069155068    pumch_lzy@163.com   
Contact: Lihong Xu, B.N.    +861069155068    xulihong1990@163.com   
Sponsors and Collaborators
Peking Union Medical College Hospital
Investigators
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Principal Investigator: Zhenyu Liu, M.D. Department of Cardiology, Peking Union Medical College Hospital

Publications:
Task Force Members, Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, Budaj A, Bugiardini R, Crea F, Cuisset T, Di Mario C, Ferreira JR, Gersh BJ, Gitt AK, Hulot JS, Marx N, Opie LH, Pfisterer M, Prescott E, Ruschitzka F, Sabaté M, Senior R, Taggart DP, van der Wall EE, Vrints CJ; ESC Committee for Practice Guidelines, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S; Document Reviewers, Knuuti J, Valgimigli M, Bueno H, Claeys MJ, Donner-Banzhoff N, Erol C, Frank H, Funck-Brentano C, Gaemperli O, Gonzalez-Juanatey JR, Hamilos M, Hasdai D, Husted S, James SK, Kervinen K, Kolh P, Kristensen SD, Lancellotti P, Maggioni AP, Piepoli MF, Pries AR, Romeo F, Rydén L, Simoons ML, Sirnes PA, Steg PG, Timmis A, Wijns W, Windecker S, Yildirir A, Zamorano JL. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013 Oct;34(38):2949-3003. doi: 10.1093/eurheartj/eht296. Epub 2013 Aug 30. Erratum in: Eur Heart J. 2014 Sep 1;35(33):2260-1.
Shah BH, Nawaz Z, Saeed SA. Gilani AH. Agonist-dependent Differential Effects of Berberine in Human Platelet Aggregation. Phytother. Res. 12, S60-S62 (1998).
Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD; Writing Group on the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction, Thygesen K, Alpert JS, White HD, Jaffe AS, Katus HA, Apple FS, Lindahl B, Morrow DA, Chaitman BA, Clemmensen PM, Johanson P, Hod H, Underwood R, Bax JJ, Bonow RO, Pinto F, Gibbons RJ, Fox KA, Atar D, Newby LK, Galvani M, Hamm CW, Uretsky BF, Steg PG, Wijns W, Bassand JP, Menasché P, Ravkilde J, Ohman EM, Antman EM, Wallentin LC, Armstrong PW, Simoons ML, Januzzi JL, Nieminen MS, Gheorghiade M, Filippatos G, Luepker RV, Fortmann SP, Rosamond WD, Levy D, Wood D, Smith SC, Hu D, Lopez-Sendon JL, Robertson RM, Weaver D, Tendera M, Bove AA, Parkhomenko AN, Vasilieva EJ, Mendis S; ESC Committee for Practice Guidelines (CPG). Third universal definition of myocardial infarction. Eur Heart J. 2012 Oct;33(20):2551-67. doi: 10.1093/eurheartj/ehs184. Epub 2012 Aug 24.

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Responsible Party: LiuZhenyu, Professor, Peking Union Medical College Hospital
ClinicalTrials.gov Identifier: NCT03378934     History of Changes
Other Study ID Numbers: 2016-I2M-1-011
JS-1375 ( Other Identifier: Ethics Committee in Peking Union Medical College Hospital )
First Posted: December 20, 2017    Key Record Dates
Last Update Posted: October 3, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by LiuZhenyu, Peking Union Medical College Hospital:
Coronary Artery Disease
Percutaneous Coronary Intervention
Antiplatelet
Berberine

Additional relevant MeSH terms:
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Aspirin
Clopidogrel
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Neurotransmitter Agents