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

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

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.

Study Overview

• Status: Completed
• Conditions: Stable Angina
• Intervention / Treatment: Drug: Placebos; Drug: clopidogrel

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.

• Study Type: Observational
• Enrollment (Actual): 35

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Taipei City Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

stable angina who received routine dual antiplatelet agents therapy.

Description

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).

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

7

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
group 1; placebo control without medication.	Drug: Placebos; no medication, healthy subjects.
group 2; hyper-reactive responser after clopidogrel.	Drug: clopidogrel; routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit)
group 3; hypo-reactive responser after clopidogrel.	Drug: clopidogrel; routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit)
group 4; normo-reactive responser after clopidogrel.	Drug: clopidogrel; routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit)
group 5; reaction after OPC-13013	Drug: clopidogrel; routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit)
group 6; reaction after AR-C	Drug: clopidogrel; routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit)
group 7; reaction after simastatin	Drug: clopidogrel; routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PRU(Platelet Rreactivity Unit) 24 Hours After DAPT(Dual AntiPlatelet Therapy) Western Blot After Medication	PRU(Platelet Rreactivity Unit) 24 hours after DAPT(Dual AntiPlatelet Therapy) Western blot after medication	24 hours

Collaborators and Investigators

• Sponsor: Taipei City Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): November 1, 2017
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: June 6, 2017
• First Submitted That Met QC Criteria: June 15, 2017
• First Posted (Actual): June 16, 2017

Study Record Updates

• Last Update Posted (Actual): November 21, 2019
• Last Update Submitted That Met QC Criteria: November 2, 2019
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: PRU; P2Y12 receptor
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina Pectoris; Angina, Stable; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: TCHIRB-10603117-E

Drug and device information, study documents

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