Genotyping GUided Antiplatelet theRapy in pAtieNts Treated With Drug Eluting stEnts (GUARANTEE)

  • STATUS
    Recruiting
  • End date
    Jan 27, 2023
  • participants needed
    3780
  • sponsor
    Beijing Anzhen Hospital
Updated on 27 January 2021
artery disease
ticagrelor
clopidogrel
percutaneous coronary intervention
antiplatelet therapy
acute coronary syndrome

Summary

The aim of this study is to assess the efficacy and safety of the CYP2C19 genotype guided antiplatelet treatment strategy, using clopidogrel in non-carriers of a CYP2C19*2 or 3 allele and ticagrelor in carriers of a CYP2C192 or *3 allele in patients treated with new generation drug eluting stents.

Description

Background: P2Y12 receptor inhibitors are crucial for the management of patients undergoing coronary stenting. Although large-scale trials have shown that ticagrelor is superior to clopidogrel in terms of platelet inhibition and reduction of major adverse cardiovascular events (MACE), clopidogrel remains the most commonly used P2Y12 receptor inhibitor due to its lower price and bleeding risk. Despite the combined use of aspirin and clopidogrel, a substantial portion of patients after coronary stenting are at increased risk for adverse cardiovascular events including death, myocardial infarction, and stent thrombosis. This phenomenon may be due to the so-called clopidogrel resistance. Cytochrome P450 2C19 (CYP2C19) polymorphism plays a crucial role in the clopidogrel resistance. CYP2C19 is responsible, in part, for converting the clopidogrel prodrug into an active metabolite that irreversibly binds to the P2Y12 receptor thus inhibiting ADP-induced platelet aggregation. CYP2C19*2 and *3, which encounter loss function, have been demonstrated to be the most common genetic variants resulting in clopidogrel resistance.

Methods: Patients who undergo coronary stenting will be randomized to a prospective CYP2C19 genotype-guided antiplatelet therapy arm versus a conventional therapy arm. Venous blood collection will be completed immediately after randomization in all patients eligible for the study. The genotype results involving CYP2C19*2 and *3 allele variants will be obtained within 48 hours only in the genotyping arm. CYP2C19 *2 or 3 reduced function allele patients will receive ticagrelor 90 mg bid, whereas non-2 or -*3 CYP2C19 patients will receive clopidogrel 75 mg once daily. The conventional therapy arm will receive either clopidogrel or ticagrelor, according to the clinical and procedural characteristics of patients. The dual antiplatelet therapy will last for at least one year in the both arms. The primary endpoints will be evaluated at one-year follow-up.

Details
Condition Stent, Drug Eluting Stent, Genotype, Acute Coronary Syndrome, Ischemic Heart Disease, Stable Angina, Stable Angina Pectoris, Cardiac Ischemia, Myocardial Ischemia, Angina, Stable, Angina, Stable, acute coronary syndromes
Treatment CYP2C19 genotype testing
Clinical Study IdentifierNCT03783351
SponsorBeijing Anzhen Hospital
Last Modified on27 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age greater than or equal to 18 yrs?
Gender: Male or Female
Do you have any of these conditions: Drug Eluting Stent or Acute Coronary Syndrome or Genotype or Angina, Stable?
Do you have any of these conditions: Acute Coronary Syndrome or Stable Angina Pectoris or Angina, Stable or Cardiac Ischemia or acute coronary syndromes or Ischemic Heart Disease or Stabl...?
Do you have any of these conditions: Ischemic Heart Disease or Myocardial Ischemia or acute coronary syndromes or Cardiac Ischemia or Angina, Stable or Stable Angina or Acute Coronary Syn...?
Do you have any of these conditions: Angina, Stable or Ischemic Heart Disease or Genotype or Stable Angina or Myocardial Ischemia or acute coronary syndromes or Stable Angina Pectoris or ...?
Patient 18 years of age
Patient presents with acute coronary syndrome (ACS) or stable coronary artery disease (SCAD)
Patient has a percutaneous coronary intervention (PCI) indication and the new generation drug eluting stent(s) is successfully implanted

Exclusion Criteria

Patient unable to receive 12 months of dual anti-platelet therapy
Patient developing procedure-related complications such as stent thrombosis, coronary dissection, coronary perforation, cardiac tamponade or no-reflow during PCI
Contraindicated or allergic to clopidogrel or ticagrelor
Patient or physician refusal to enroll in the study
Patient having received thrombolytic therapy within the previous 24 hours
Physician has known the patient's CYP2C19 genotype
Anticipated discontinuation of dual anti-platelet therapy within the 12-month follow-up period, example for elective surgery
History of intracranial hemorrhage
Patient has a history of bleeding diathesis or coagulopathy
Patient has an active pathological bleeding, such as active gastrointestinal (GI) bleeding
Patient is pregnant, breastfeeding, or planning to become pregnant within 12 months
Patient is receiving chronic oral anticoagulation therapy (i.e., vitamin K antagonist, direct thrombin inhibitor, Factor Xa inhibitor)
Patient with cardiogenic shock or mechanical circulatory assist devices placed
Patient with LVEF <30%
Patient with active liver diseases
Patient with severe renal insufficiency (eGFR <30ml/min/1.73m2 based on simplified MDRD equation or CrCl <30ml/min based on Cockcroft-Gault equation)
Patient has a malignancy or a life expectancy of less than one year
Platelet count <100 000/L, or hematocrit <32% or >52%, or white blood cell count <3000/L
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