Downstream Molecular Signals of P2Y12 Receptors in Hyporeactive Patients Under Clopidogrel Treatment A Possible Mechanism of HOTPR(High On-Treatment Platelet Reactivity)

NCT ID: NCT03190005

Last Updated: 2019-11-21

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 35 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2017-01-01
• Study Completion Date: 2017-11-01

Brief Summary

The investigators designed the following experiment to observe the pattern of administration in vitro, which can be completely excluded liver enzyme cytochrome P450 metabolism under the influence and observe the relevant P2Y12 receptor downstream signal changes, hope in the above experiments, that the human body directly for the difference between the existence of drug reactions exist.

Detailed Description

Platelet reactivity has been accepted as an indicator of the reaction of the P2Y12 inhibitor during treatment, currently, the existing evidence to support the post-treatment platelet activity can be used to distinguish the potential risk among patients who received percutaneous transluminal coronary angioplasty after ischemic / thrombotic events. The risks of stent thrombosis, of which, by analysis of the PRU (P2Y12 reaction units) value level of VerifyNow System has been considered an international standard tools. PRU value by VerifyNow system can easily and quickly showed platelet reactivity relative to short or long term risk stratification under dual antiplatelet agents(aspirin and clopidogrel) after stents implantation. High PRU response units (drug poor responders) in accordance with the 2013 publication of the European Society of Cardiology guidelines defined of platelet function, is PRU not less than 208(≥208).

The investigators ran a previous related plan within 2014 under the medical study project budget of the Taipei City hospital, which named "platelet reactivity as a post-percutaneous coronary stent implantation antiplatelet adjust the reference", it has been figured that responsibility under the P2Y12 receptor inhibitors were significantly different between the taiwanese and Caucasians (taiwanese revealed clopidogrel lower responsive, but stronger reaction to ticagrelor), although "low" response to clopidogrel between taiwanese (In fact, according to our experiments, 30 days after medication, the rate of HOTPR-High On- Treatment Platelet Reactivity; namely PRU≥208, the taiwanese and Caucasians are very close to each), but it has relative lower subacute stent thrombosis rate than the Caucasian at 30 days(This reaction is also known as the "Asian paradox" ), according to literature known abroad because of the high prevalence of CYP2C19 point gene deletion rate among the Asians (compare with Caucasians: ~ 65% vs ~ 30%); there also suggested other possible explanations: Caucasian factor V Leiden (G1691A) and prothrombin (G20210A) a higher proportion of mutations, on hemostatic factors (fibrinogen, d-dimer, and factor VIII) and plasma endothelial activation markers (such as von Willebrand factor, intercellular adhesion molecule 1, and E-selectin) existed differences between the races; in addition, a number of different indicators of inflammation, such as CRP. Asians show lower level CRP than the Caucasians. However, did the investigators found the true answer? So, the investigators designed the following experiment, through the mode of drug administration in vitro, can completely exclude the influence of the liver metabolic enzyme cytochrome P450, and observe the relevant downstream signals of P2Y12 receptors. The investigators believed through the current study, the internal differences in drug responsibility can be clarified.

Conditions

Stable Angina

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

group 1

placebo control without medication.

Placebos

Intervention Type: DRUG

no medication, healthy subjects.

group 2

hyper-reactive responser after clopidogrel.

clopidogrel

Intervention Type: DRUG

routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit)

group 3

hypo-reactive responser after clopidogrel.

clopidogrel

Intervention Type: DRUG

routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit)

group 4

normo-reactive responser after clopidogrel.

clopidogrel

Intervention Type: DRUG

routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit)

group 5

reaction after OPC-13013

clopidogrel

Intervention Type: DRUG

routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit)

group 6

reaction after AR-C

clopidogrel

Intervention Type: DRUG

routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit)

group 7

reaction after simastatin

clopidogrel

Intervention Type: DRUG

routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit)

Interventions

clopidogrel

routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit)

Intervention Type: DRUG

Placebos

no medication, healthy subjects.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• DAPT(Dual antiplatelet therapy) after regular stent implantation.

Exclusion Criteria

• allergy to DAPT(Dual antiplatelet therapy). major bleeding intolerance to DAPT(Dual antiplatelet therapy).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Taipei City Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Yueh-Chung, Chen

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Taipei city hospital

Taipei, , Taiwan

Countries

Taiwan

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Document Type: Study Protocol

View Document

Other Identifiers

TCHIRB-10603117-E

Identifier Type: -

Identifier Source: org_study_id