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

Stable Angina Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03190005
• Other study ID #: TCHIRB-10603117-E
• Status: Completed
• Start date: January 1, 2017
• Est. completion date: November 1, 2017

Study information

• Verified date: June 2017
• Source: Taipei City Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: November 1, 2017
• Est. primary completion date: November 1, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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).

Related Conditions & MeSH terms

• Angina, Stable
• Stable Angina

Intervention

Drug:
• clopidogrel
routine Dual antiplatelet therapy after stent implantation, then check PRU(platelet reactivity unit)
• Placebos
no medication, healthy subjects.

Locations

Country	Name	City	State
Taiwan	Taipei city hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Taipei City Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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