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

Phase 4

• Conditions: Coronary Artery Disease; Myocardial Infarction; Vascular Disease; Angina Pectoris; Cardiovascular Disease; Ischemia; Infarction; Embolism; Thrombosis; Chest Pain
• Interventions: Drug: clopidogrel; Drug: Ticagrelor or prasugrel

• Registration Number: NCT01823185
• Lead Sponsor: Imam Abdulrahman Bin Faisal University

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2013-03
• Study First Submitted: 2013-03-19
• Study First Submitted QC: 2013-04-02
• Study First Posted: 2013-04-04
• Status Verified: 2016-01
• Primary Completion: 2016-01
• Last Update Submitted: 2016-01-20
• Last Update Posted: 2016-01-22
• Study Completion: 2016-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 1500

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Clopidogrel	clopidogrel	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.
Ticagrelor or prasugrel	Ticagrelor or prasugrel	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.

Primary Outcome Measures

Name	Time	Method
cardiovascular event	1 year	The primary end point is the number of patients who develop adverse major cardiovascular event which include recurrent myocardial infarction, non-fatal stroke, cardiovascular mortality, severe ischemia, major bleeding at 30days after PCI.

Secondary Outcome Measures

Name	Time	Method
Mortality	30 days and 1 year	Secondary efficacy endpoints are the number of patients who either died , died from cardiovascular death, from cerebrovascular death, developed recurrent MI, stent thrombosis, underwent urgent target vessel revascularization, developed stroke or combination of above

Trial Locations

Locations (4)

Prince Sultan Cardiac center; 🇸🇦 Al-Hasa, Saudi Arabia

Saud Al-Babtain Cardiac Center; 🇸🇦 Dammam, Saudi Arabia

King Fahd Military Medical Complex; 🇸🇦 Dammam, Saudi Arabia

King Fahd University Hospital; 🇸🇦 Al-Khobar, Saudi Arabia