Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03783351
Recruitment Status : Not yet recruiting
First Posted : December 21, 2018
Last Update Posted : March 6, 2019
Sponsor:
Information provided by (Responsible Party):
Yujie Zhou, Beijing Anzhen Hospital

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

Condition or disease Intervention/treatment Phase
Angina, Stable Acute Coronary Syndrome Drug-Eluting Stents Genotype Genetic: CYP2C19 genotype testing Phase 4

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3780 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: CYP2C19 Genotype-GUided Dual Antiplatelet theRapy in pAtieNts Treated With New Generation Drug Eluting stEnts (the GUARANTEE Study)
Estimated Study Start Date : April 2019
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : April 2021

Resource links provided by the National Library of Medicine


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:
  • clopidogrel
  • ticagrelor




Primary Outcome Measures :
  1. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03783351


Contacts
Layout table for location contacts
Contact: Yujie Zhou, PhD,MD 8613901330652 azzyj12@163.com

Locations
Layout table for location information
China, Beijing
Beijing Anzhen Hospital Not yet recruiting
Beijing, Beijing, China, 100029
Contact: Yujie Zhou, PhD, MD    8613901330652    azzyj12@163.com   
Contact: Xiaoteng Ma, MD    8618810616459    maxiaotengai@163.com   
Principal Investigator: Yujie Zhou, PhD, MD         
Sub-Investigator: Xiaoli Liu, PhD, MD         
Peking Union Medical College Hospital Not yet recruiting
Beijing, Beijing, China, 100032
Contact: Zhujun Shen, PhD, MD    8613801199495    zhujun66shen@126.com   
Principal Investigator: Zhujun Shen, PhD, MD         
Fuwai Hospital Chinese Academy of Medical Sciences Not yet recruiting
Beijing, Beijing, China, 100037
Contact: Yanmin Yang, PhD, MD    8613501241275    yymfuwai@163.com   
Principal Investigator: Yanmin Yang, PhD, MD         
Beijing Friendship Hospital Not yet recruiting
Beijing, Beijing, China, 100050
Contact: Hongwei Li, PhD, MD    8613801396679    lhw19656@sina.com   
Principal Investigator: Hongwei Li, PhD, MD         
Beijing Tian Tan Hospital Not yet recruiting
Beijing, Beijing, China, 100070
Contact: Zening Jin, PhD, MD    8613581775428    jinzening@hotmail.com   
Principal Investigator: Zening Jin, PhD, MD         
Beijing Tong Ren Hospital Not yet recruiting
Beijing, Beijing, China, 100730
Contact: Xubo Shi, PhD, MD    8613601217923    shixubo@vip.sina.com   
Principal Investigator: Xubo Shi, PhD, MD         
Beijing LuHe Hospital Not yet recruiting
Beijing, Beijing, China, 101199
Contact: Jincheng Guo, PhD, MD    8613521968844    guojcmd@126.com   
Principal Investigator: Jincheng Guo, PhD, MD         
Sponsors and Collaborators
Beijing Anzhen Hospital
Investigators
Layout table for investigator information
Study Chair: Yujie Zhou, PhD,MD Beijing Anzhen Hospital

Layout table for additonal information
Responsible Party: Yujie Zhou, Professor, Beijing Anzhen Hospital
ClinicalTrials.gov Identifier: NCT03783351     History of Changes
Other Study ID Numbers: GUARANTEE
First Posted: December 21, 2018    Key Record Dates
Last Update Posted: March 6, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Acute Coronary Syndrome
Angina, Stable
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Angina Pectoris
Chest Pain
Pain
Neurologic Manifestations
Signs and Symptoms
Clopidogrel
Ticagrelor
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs