Bedside Testing of CYP2C19 Gene for Treatment of Patients With PCI With Antiplatelet Therapy

Imam Abdulrahman Bin Faisal University

Status and phase: Unknown; Phase 4

Conditions: Infarction; Coronary Artery Disease; Embolism; Vascular Disease; Thrombosis; Chest Pain; Ischemia; Angina Pectoris; Myocardial Infarction; Heart Disease; Cardiovascular Disease

Treatments: Drug: Ticagrelor or prasugrel; Drug: clopidogrel

Study type: Interventional

Funder types: Other

Identifiers

NCT01823185

STGUD005

Details and patient eligibility

About

Clopidogrel is crucial as antiplatelet treatment in patients undergoing percutaneous coronary intervention (PCI) with stent implantation and during one year after PCI, to prevent atherothrombotic complications. However, clopidogrel is ineffective in certain patients due to genetic mutation in CYP2C19 gene a specific enzyme in the liver required for metabolism of clopidogrel. Therefore, the purpose of this study is to test these patients genetically at bedside and prescribe an alternative drug such as Ticagrelor (90 mg twice daily) or prasugrel ( 10mg once daily or 5mg once daily if the patient older than 75 years or a body weight < 60kg) if they are carriers of the allele 2 or 3 of the mutated gene.

Full description

Clopidogrel is crucial as antiplatelet treatment in patients undergoing percutaneous coronary intervention (PCI) with stent implantation and during one year after PCI, to prevent atherothrombotic complications. Clopidogrel is converted into its active metabolite by Cytochrome P2C19 (CYP2C19). However 30 % of the Saudi population is carrier of the non functional CYP2C19*2 or *3 alleles having an impaired CYP2C19 capacity, resulting in decreased effectiveness of Clopidogrel. These patients have a 42% higher risk for major cardiovascular events (MACE) compared to non carriers. Further 50 % of the MACE occurs in the first 48 hours. Therefore Ticagrelor (90 mg twice daily) or prasugrel ( 10mg once daily or 5mg once daily if the patient older than 75 years or a body weight < 60kg) whose actions are not dependent on conversion by CYP2C19 may be an alternative only in carriers of the non functional CYP2C19*2 or *3 alleles. This might be cost effective and prevent patients form MACE. Therefore the objective of this study is to assess the efficacy, complication free survival, safety and cost-effectiveness of the CYP2C19 genotype guided antiplatelet treatment strategy, using clopidogrel or prasugrel (or Ticlid). All participants will be followed for one year using follow up questionnaires.

Enrollment: 1,500 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Male & female age 18-70 years

Inclusion Criteria:

• Patient presents with acute myocardial infarction of more than 30 minutes and less than 12 hours
• Patient eligible for PCI

Exclusion Criteria:

• Life expectancy of less than one year
• Previously Known genotype
• Receiving chemotherapy for malignancy
• On dialysis or receiving immunosuppressive therapy or have autoimmune disease
• Hepatic impairment
• History of bleeding diathesis
• Receiving vitamin K antagonist therapy
• Confirmed hypertension
• Out of normal range platelet count
• History of major surgery
• Severe trauma or fracture
• Pregnancy and lactation
• Concomitant use of simvastatin, cytochrome P450 3A4 inhibitors or inducers
• Hypersensitivity to clopidogrel or ticagrelor or prasugrel

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,500 participants in 2 patient groups

Clopidogrel

Active Comparator group

Description:

CYP2C19 genotyping will be carried out at the end of the study period. Clopidogrel will be used for treatment for one year according to local protocol. Patients will receive clopidogrel 75 mg per day.

Treatment:

Drug: clopidogrel

Ticagrelor or prasugrel

Experimental group

Description:

Ticagrelor (90 mg twice daily) or prasugrel ( 10mg once daily or 5mg once daily if the patient older than 75 years or a body weight \< 60kg) according to local protocol.

Treatment:

Drug: Ticagrelor or prasugrel