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

September 27, 2023 updated by: Yujie Zhou, Beijing Anzhen Hospital

CYP2C19 Genotype-GUided Dual Antiplatelet theRapy in pAtieNts Treated With New Generation Drug Eluting stEnts (the GUARANTEE Study)

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 CYP2C19*2 or *3 allele in patients treated with new generation drug eluting stents.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

4009

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Yujie Zhou, PhD, MD
  • Phone Number: 8613901330652
  • Email: azzyj12@163.com

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100032
        • Recruiting
        • Peking Union Medical College Hospital
        • Contact:
        • Principal Investigator:
          • Zhujun Shen, PhD, MD
      • Beijing, Beijing, China
        • Recruiting
        • China-Japan Friendship Hospital
        • Contact:
        • Principal Investigator:
          • Jingang Zheng, PhD, MD
      • Beijing, Beijing, China, 100050
        • Recruiting
        • Beijing Friendship Hospital
        • Contact:
        • Principal Investigator:
          • Hui Chen, PhD, MD
      • Beijing, Beijing, China, 100029
        • Recruiting
        • Beijing Anzhen Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Yujie Zhou, PhD, MD
        • Sub-Investigator:
          • Xiaoli Liu, PhD, MD
      • Beijing, Beijing, China, 100000
        • Recruiting
        • Beijing Chaoyang Hospital
        • Contact:
        • Principal Investigator:
          • Xinchun Yang, PhD, MD
      • Beijing, Beijing, China, 100070
        • Withdrawn
        • Beijing Tian Tan Hospital
      • Beijing, Beijing, China, 100730
        • Recruiting
        • Beijing Tong Ren Hospital
        • Contact:
        • Principal Investigator:
          • Xubo Shi, PhD, MD
      • Beijing, Beijing, China, 101199
        • Recruiting
        • Beijing luhe hospital
        • Contact:
        • Principal Investigator:
          • Jincheng Guo, PhD, MD
      • Beijing, Beijing, China, 100037
        • Completed
        • Fuwai Hospital Chinese Academy of Medical Sciences
      • Beijing, Beijing, China, 102218
        • Completed
        • Beijing Tsinghua Changgung Hospital
    • Jiangsu
      • Xuzhou, Jiangsu, China, 221002
        • Withdrawn
        • The Affiliated Hospital of Xuzhou Medical University
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • Withdrawn
        • West China Hospital Sichuan University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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/μL, or hematocrit <32% or >52%, or white blood cell count <3000/μL

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Conventional Therapy
Patients randomized to the Conventional Therapy arm will receive either clopidogrel or ticagrelor, according to the clinical and procedural characteristics of patients. CYP2C19 genotyping will be performed at the end of study.
Active Comparator: CYP2C19 Genotyping
CYP2C19 genotyping will be performed within 48 hours after randomization. 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.
Genetic: CYP2C19 genotype testing
CYP2C19 genotype testing will be conducted in a designated central laboratory.
Other Names:
  • ticagrelor
  • clopidogrel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurrence of main adverse cardiovascular and cerebrovascular events (MACCE)
Time Frame: 1 year
MACCE will include all-cause death, non-fatal stroke, non-fatal myocardial infarction (MI) and ischemia driven revascularization at one-year follow-up.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Anzhen Hospital

Investigators

  • Study Chair: Yujie Zhou, PhD,MD, Beijing Anzhen Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 27, 2019

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

February 1, 2025

Study Registration Dates

First Submitted

December 11, 2018

First Submitted That Met QC Criteria

December 19, 2018

First Posted (Actual)

December 21, 2018

Study Record Updates

Last Update Posted (Actual)

September 28, 2023

Last Update Submitted That Met QC Criteria

September 27, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GUARANTEE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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