Coronary Artery DiseasePhase 4APLABE-PCINCT03378934
Anti-platelet Effect of Berberine in Patients After Percutaneous Coronary Intervention
A Phase 4 study testing Berberine, Standard treatment and Aspirin in people with Coronary Artery Disease and Percutaneous Coronary Intervention, run by Peking Union Medical College Hospital at 1 site in China.
Trial 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 percutaneous coronary intervention. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Coronary Artery Disease, Percutaneous Coronary Intervention
- What is being tested?
- Berberine, Standard treatment and Aspirin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 siteChina
- Study dates
- 26 Sep 2018to Aug 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of written informed consent.
- Aged 18-70 years, male or female.
- Currently, > 8 but ≤ 40 weeks after index percutaneous coronary intervention (PCI) .
- Receiving dual antiplatelet therapy (DAPT) with aspirin (Bayaspirin TM) 100 mg once daily and clopidogrel (Plavix TM) 75 mg once daily for ≥ 7 days.
- 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;
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- Bleeding events include major or minor bleeding according to the Platelet Inhibition and Patient Outcomes (PLATO) definition.
- PRECISE-DAPT score < 25 evaluated after the index PCI and before the index hospital discharge.
- Females who are either post-menopausal > 1 year or surgically sterile.
Who cannot join
- Use of berberine within 30 days of screening.
- Use of any fibrinolytic or antithrombotic agents, with the exception of aspirin and clopidogrel, within 30 days of screening.
- 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.
- Planned use of berberine, as well as any fibrinolytic or antithrombotic agents, with the exception of aspirin (Bayaspirin TM) and clopidogrel (Plavix TM), during the study period.
- 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.
- Planned coronary revascularization, including PCI and coronary artery bypass graft (CABG) during the study period.
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- 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.
- 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.
- History of intolerance to aspirin, clopidogrel, and berberine.
- 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.
- Patients who has previously been randomized in this study.
- Participation in another investigational drug or device study within 30 days of screening.
- Involvement in the planning and conduct of the study (applies to investigators, contract research organization staff, and study site staff, et al).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730
Zhenyu Liu, M.D., +861069155068, pumch_lzy@163.com
Lihong Xu, B.N., +861069155068, xulihong1990@163.com
About this study
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 Percutaneous Coronary Intervention
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 percutaneous coronary intervention.
Read the detailed description
Background
Dual antiplatelet therapy (DAPT) with aspirin and a platelet P2Y12 inhibitor is mandatory in patients after percutaneous coronary intervention (PCI). 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 PCI 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 PCI.
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 together 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 PCI. The result of the present study would provide pharmacodynamical data for the design of future outcome studies.
- Being tested
- Berberine, Standard treatment, Aspirin, Clopidogrel
- Keywords
- Coronary Artery Disease, Percutaneous Coronary Intervention, Antiplatelet, Berberine
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BerberineDrug
Also called Berberine Hydrochloride Tablets
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).
Standard treatment for 12±1 weeks.
AspirinDrug
Also called Aspirin Enteric-coated Tablets, Bayaspirin
Aspirin 100 mg once daily for 12±1 weeks.
ClopidogrelDrug
Also called Clopidogrel Hydrogen Sulphate Tablets, Plavix
Clopidogrel 75 mg once daily for 12±1 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Berberine Arm | Experimental | 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. Receives: Drug: Berberine; Drug: Standard treatment; Drug: Aspirin; Drug: Clopidogrel |
| Control Arm | Active comparator | 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. Receives: Drug: Standard treatment; Drug: Aspirin; Drug: Clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
P2Y12 reaction unit (PRU)
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
Measured: On the 12th (11th-13th) week of treatment
Secondary outcomes (8)
P2Y12 reaction unit (PRU)
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 ]
Measured: On the 8th (7th-9th) week of treatment
P2Y12 reaction unit (PRU)
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 ]
Measured: On the 4th (3rd-5th) week of treatment
Platelet reactivity index (PRI)
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 ]
Measured: On the 12th (11th-13th) week of treatment
Platelet reactivity index (PRI)
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 ]
Measured: On the 8th (7th-9th) week of treatment
Platelet reactivity index (PRI)
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 ]
Measured: On the 4th (3rd-5th) week of treatment
Urinary 11-dehydro-thromboxane B2 (11-dH-TXB2)
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 ]
Measured: On the 12th (11th-13th) week of treatment
Urinary 11-dehydro-thromboxane B2 (11-dH-TXB2)
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 ]
Measured: On the 8th (7th-9th) week of treatment
Urinary 11-dehydro-thromboxane B2 (11-dH-TXB2)
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 ]
Measured: On the 4th (3rd-5th) week of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2017
- Study start26 Sep 2018
- Primary completionJun 2026 (estimated)
- Study completionAug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (56)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, LiuZhenyu, Peking Union Medical College Hospital
- Investigators
- Zhenyu Liu, M.D., Principal investigator, Department of Cardiology, Peking Union Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03378934
- Sponsor's protocol ID
- 2016-I2M-1-011
- Other IDs
- JS-1375
- Acronym
- APLABE-PCI
- Status last verified
- Nov 2025
- First submitted
- 14 Dec 2017
- Last updated
- 19 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Amsterdam EA, Wenger NK, Brindis RG, Casey DE Jr, Ganiats TG, Holmes DR Jr, Jaffe AS, Jneid H, Kelly RF, Kontos MC, Levine GN, Liebson PR, Mukherjee D, Peterson ED, Sabatine MS, Smalling RW, Zieman SJ. 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014 Dec 23;64(24):e139-e228. doi: 10.1016/j.jacc.2014.09.017. Epub 2014 Sep 23. No abstract available.
PubMed 25260718Aradi D, Komocsi A, Vorobcsuk A, Rideg O, Tokes-Fuzesi M, Magyarlaki T, Horvath IG, Serebruany VL. Prognostic significance of high on-clopidogrel platelet reactivity after percutaneous coronary intervention: systematic review and meta-analysis. Am Heart J. 2010 Sep;160(3):543-51. doi: 10.1016/j.ahj.2010.06.004.
PubMed 20826265Aradi D, Storey RF, Komocsi A, Trenk D, Gulba D, Kiss RG, Husted S, Bonello L, Sibbing D, Collet JP, Huber K; Working Group on Thrombosis of the European Society of Cardiology. Expert position paper on the role of platelet function testing in patients undergoing percutaneous coronary intervention. Eur Heart J. 2014 Jan;35(4):209-15. doi: 10.1093/eurheartj/eht375. Epub 2013 Sep 25. No abstract available.
PubMed 24067509Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC, Magnani G, Bansilal S, Fish MP, Im K, Bengtsson O, Oude Ophuis T, Budaj A, Theroux P, Ruda M, Hamm C, Goto S, Spinar J, Nicolau JC, Kiss RG, Murphy SA, Wiviott SD, Held P, Braunwald E, Sabatine MS; PEGASUS-TIMI 54 Steering Committee and Investigators. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015 May 7;372(19):1791-800. doi: 10.1056/NEJMoa1500857. Epub 2015 Mar 14.
PubMed 25773268Bonello L, Camoin-Jau L, Arques S, Boyer C, Panagides D, Wittenberg O, Simeoni MC, Barragan P, Dignat-George F, Paganelli F. Adjusted clopidogrel loading doses according to vasodilator-stimulated phosphoprotein phosphorylation index decrease rate of major adverse cardiovascular events in patients with clopidogrel resistance: a multicenter randomized prospective study. J Am Coll Cardiol. 2008 Apr 8;51(14):1404-11. doi: 10.1016/j.jacc.2007.12.044.
PubMed 18387444Brar SS, ten Berg J, Marcucci R, Price MJ, Valgimigli M, Kim HS, Patti G, Breet NJ, DiSciascio G, Cuisset T, Dangas G. Impact of platelet reactivity on clinical outcomes after percutaneous coronary intervention. A collaborative meta-analysis of individual participant data. J Am Coll Cardiol. 2011 Nov 1;58(19):1945-54. doi: 10.1016/j.jacc.2011.06.059.
PubMed 22032704Caliceti C, Franco P, Spinozzi S, Roda A, Cicero AF. Berberine: New Insights from Pharmacological Aspects to Clinical Evidences in the Management of Metabolic Disorders. Curr Med Chem. 2016;23(14):1460-76. doi: 10.2174/0929867323666160411143314.
PubMed 27063256Chen JJ, Chang YL, Teng CM, Lin WY, Chen YC, Chen IS. A new tetrahydroprotoberberine N-oxide alkaloid and anti-platelet aggregation constituents of Corydalis tashiroi. Planta Med. 2001 Jul;67(5):423-7. doi: 10.1055/s-2001-15820.
PubMed 11488455Chu JW, Wong CK, Chambers J, Wout JV, Herbison P, Tang EW. Aspirin resistance determined from a bed-side test in patients suspected to have acute coronary syndrome portends a worse 6 months outcome. QJM. 2010 Jun;103(6):405-12. doi: 10.1093/qjmed/hcq038. Epub 2010 Mar 30.
PubMed 20356848Combescure C, Fontana P, Mallouk N, Berdague P, Labruyere C, Barazer I, Gris JC, Laporte S, Fabbro-Peray P, Reny JL; CLOpidogrel and Vascular ISchemic Events Meta-analysis Study Group. Clinical implications of clopidogrel non-response in cardiovascular patients: a systematic review and meta-analysis. J Thromb Haemost. 2010 May;8(5):923-33. doi: 10.1111/j.1538-7836.2010.03809.x. Epub 2010 Feb 12.
PubMed 20156305Fritsma GA, Ens GE, Alvord MA, Carroll AA, Jensen R. Monitoring the antiplatelet action of aspirin. JAAPA. 2001 May;14(5):57-8, 61-2. No abstract available.
PubMed 11523339Glauser J, Emerman CL, Bhatt DL, Peacock WF 4th. Platelet aspirin resistance in ED patients with suspected acute coronary syndrome. Am J Emerg Med. 2010 May;28(4):440-4. doi: 10.1016/j.ajem.2009.01.004.
PubMed 20466222Gurbel PA, Bliden KP, Butler K, Tantry US, Gesheff T, Wei C, Teng R, Antonino MJ, Patil SB, Karunakaran A, Kereiakes DJ, Parris C, Purdy D, Wilson V, Ledley GS, Storey RF. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009 Dec 22;120(25):2577-85. doi: 10.1161/CIRCULATIONAHA.109.912550. Epub 2009 Nov 18.
PubMed 19923168Gurbel PA, Bliden KP, Butler K, Antonino MJ, Wei C, Teng R, Rasmussen L, Storey RF, Nielsen T, Eikelboom JW, Sabe-Affaki G, Husted S, Kereiakes DJ, Henderson D, Patel DV, Tantry US. Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: the RESPOND study. Circulation. 2010 Mar 16;121(10):1188-99. doi: 10.1161/CIRCULATIONAHA.109.919456. Epub 2010 Mar 1.
PubMed 20194878Huang CG, Chu ZL, Wei SJ, Jiang H, Jiao BH. Effect of berberine on arachidonic acid metabolism in rabbit platelets and endothelial cells. Thromb Res. 2002 May 15;106(4-5):223-7. doi: 10.1016/s0049-3848(02)00133-0.
PubMed 12297129
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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 Percutaneous Coronary Intervention
- ClinicalTrials.gov ID
- NCT03378934
- Acronym / sponsor ID
- APLABE-PCI / 2016-I2M-1-011
- Keywords
- Coronary Artery Disease, Percutaneous Coronary Intervention, Antiplatelet, Berberine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Study start
- 26 Sep 2018 (actual)
- Primary completion
- Jun 2026 (estimated)
- Study completion
- Aug 2026 (estimated)
- First posted
- 20 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 percutaneous coronary intervention.
Detailed description
Background
Dual antiplatelet therapy (DAPT) with aspirin and a platelet P2Y12 inhibitor is mandatory in patients after percutaneous coronary intervention (PCI). 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 PCI 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 PCI.
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 together 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 PCI. The result of the present study would provide pharmacodynamical data for the design of future outcome studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Berberine Arm | Experimental | Drug: Berberine, Drug: Standard treatment, Drug: Aspirin, Drug: ClopidogrelIn 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. |
| Control Arm | Active comparator | Drug: Standard treatment, Drug: Aspirin, Drug: ClopidogrelIn the Control Arm, patients will receive standard treatment, including aspirin 100 mg once daily and clopidogrel 75 mg once daily for 12±1 weeks. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Provision of written informed consent.
- Aged 18-70 years, male or female.
- Currently, > 8 but ≤ 40 weeks after index percutaneous coronary intervention (PCI) .
- Receiving dual antiplatelet therapy (DAPT) with aspirin (Bayaspirin TM) 100 mg once daily and clopidogrel (Plavix TM) 75 mg once daily for ≥ 7 days.
- No cardiac ischemic events or bleeding events occurred after the index PCI.
Key exclusion criteria (21 listed)
- Use of berberine within 30 days of screening.
- Use of any fibrinolytic or antithrombotic agents, with the exception of aspirin and clopidogrel, within 30 days of screening.
- 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.
- Planned use of berberine, as well as any fibrinolytic or antithrombotic agents, with the exception of aspirin (Bayaspirin TM) and clopidogrel (Plavix TM), during the study period.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BerberineAlso: Berberine Hydrochloride TabletsBerberine 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). | Drug | Berberine Arm |
| Standard treatmentStandard treatment for 12±1 weeks. | Drug | Berberine Arm, Control Arm |
| AspirinAlso: Aspirin Enteric-coated Tablets, BayaspirinAspirin 100 mg once daily for 12±1 weeks. | Drug | Berberine Arm, Control Arm |
| ClopidogrelAlso: Clopidogrel Hydrogen Sulphate Tablets, PlavixClopidogrel 75 mg once daily for 12±1 weeks. | Drug | Berberine Arm, Control Arm |
Primary outcome
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
8 secondary outcomes
P2Y12 reaction unit (PRU)
Time frame: On the 8th (7th-9th) week of treatment
P2Y12 reaction unit (PRU)
Time frame: On the 4th (3rd-5th) week of treatment
Platelet reactivity index (PRI)
Time frame: On the 12th (11th-13th) week of treatment
Platelet reactivity index (PRI)
Time frame: On the 8th (7th-9th) week of treatment
Platelet reactivity index (PRI)
Time frame: 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
Urinary 11-dehydro-thromboxane B2 (11-dH-TXB2)
Time frame: 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2025.
- Background: PubMed 25260718Amsterdam EA, Wenger NK, Brindis RG, Casey DE Jr, Ganiats TG, Holmes DR Jr, Jaffe AS, Jneid H, Kelly RF, Kontos MC, Levine GN, Liebson PR, Mukherjee D, Peterson ED, Sabatine MS, Smalling RW, Zieman SJ. 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014 Dec 23;64(24):e139-e228. doi: 10.1016/j.jacc.2014.09.017. Epub 2014 Sep 23. No abstract available.
- Background: PubMed 20826265Aradi D, Komocsi A, Vorobcsuk A, Rideg O, Tokes-Fuzesi M, Magyarlaki T, Horvath IG, Serebruany VL. Prognostic significance of high on-clopidogrel platelet reactivity after percutaneous coronary intervention: systematic review and meta-analysis. Am Heart J. 2010 Sep;160(3):543-51. doi: 10.1016/j.ahj.2010.06.004.
- Background: PubMed 24067509Aradi D, Storey RF, Komocsi A, Trenk D, Gulba D, Kiss RG, Husted S, Bonello L, Sibbing D, Collet JP, Huber K; Working Group on Thrombosis of the European Society of Cardiology. Expert position paper on the role of platelet function testing in patients undergoing percutaneous coronary intervention. Eur Heart J. 2014 Jan;35(4):209-15. doi: 10.1093/eurheartj/eht375. Epub 2013 Sep 25. No abstract available.
- Background: PubMed 25773268Bonaca MP, Bhatt DL, Cohen M, Steg PG, Storey RF, Jensen EC, Magnani G, Bansilal S, Fish MP, Im K, Bengtsson O, Oude Ophuis T, Budaj A, Theroux P, Ruda M, Hamm C, Goto S, Spinar J, Nicolau JC, Kiss RG, Murphy SA, Wiviott SD, Held P, Braunwald E, Sabatine MS; PEGASUS-TIMI 54 Steering Committee and Investigators. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015 May 7;372(19):1791-800. doi: 10.1056/NEJMoa1500857. Epub 2015 Mar 14.
- Background: PubMed 18387444Bonello L, Camoin-Jau L, Arques S, Boyer C, Panagides D, Wittenberg O, Simeoni MC, Barragan P, Dignat-George F, Paganelli F. Adjusted clopidogrel loading doses according to vasodilator-stimulated phosphoprotein phosphorylation index decrease rate of major adverse cardiovascular events in patients with clopidogrel resistance: a multicenter randomized prospective study. J Am Coll Cardiol. 2008 Apr 8;51(14):1404-11. doi: 10.1016/j.jacc.2007.12.044.
- Background: PubMed 22032704Brar SS, ten Berg J, Marcucci R, Price MJ, Valgimigli M, Kim HS, Patti G, Breet NJ, DiSciascio G, Cuisset T, Dangas G. Impact of platelet reactivity on clinical outcomes after percutaneous coronary intervention. A collaborative meta-analysis of individual participant data. J Am Coll Cardiol. 2011 Nov 1;58(19):1945-54. doi: 10.1016/j.jacc.2011.06.059.
- Background: PubMed 27063256Caliceti C, Franco P, Spinozzi S, Roda A, Cicero AF. Berberine: New Insights from Pharmacological Aspects to Clinical Evidences in the Management of Metabolic Disorders. Curr Med Chem. 2016;23(14):1460-76. doi: 10.2174/0929867323666160411143314.
- Background: PubMed 11488455Chen JJ, Chang YL, Teng CM, Lin WY, Chen YC, Chen IS. A new tetrahydroprotoberberine N-oxide alkaloid and anti-platelet aggregation constituents of Corydalis tashiroi. Planta Med. 2001 Jul;67(5):423-7. doi: 10.1055/s-2001-15820.
- Background: PubMed 20356848Chu JW, Wong CK, Chambers J, Wout JV, Herbison P, Tang EW. Aspirin resistance determined from a bed-side test in patients suspected to have acute coronary syndrome portends a worse 6 months outcome. QJM. 2010 Jun;103(6):405-12. doi: 10.1093/qjmed/hcq038. Epub 2010 Mar 30.
- Background: PubMed 20156305Combescure C, Fontana P, Mallouk N, Berdague P, Labruyere C, Barazer I, Gris JC, Laporte S, Fabbro-Peray P, Reny JL; CLOpidogrel and Vascular ISchemic Events Meta-analysis Study Group. Clinical implications of clopidogrel non-response in cardiovascular patients: a systematic review and meta-analysis. J Thromb Haemost. 2010 May;8(5):923-33. doi: 10.1111/j.1538-7836.2010.03809.x. Epub 2010 Feb 12.
- Background: PubMed 11523339Fritsma GA, Ens GE, Alvord MA, Carroll AA, Jensen R. Monitoring the antiplatelet action of aspirin. JAAPA. 2001 May;14(5):57-8, 61-2. No abstract available.
- Background: PubMed 20466222Glauser J, Emerman CL, Bhatt DL, Peacock WF 4th. Platelet aspirin resistance in ED patients with suspected acute coronary syndrome. Am J Emerg Med. 2010 May;28(4):440-4. doi: 10.1016/j.ajem.2009.01.004.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Zhenyu Liu, M.D. principal investigator
Department of Cardiology, Peking Union Medical College Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Berberine, Standard treatment and Aspirin in people with Coronary Artery Disease and Percutaneous Coronary Intervention, run by Peking Union Medical College Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zhenyu Liu, M.D. (+861069155068, pumch_lzy@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
P2Y12 reaction unit (PRU) (time frame: On the 12th (11th-13th) week of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03378934, which also lists 56 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2025.