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

Sponsor

Imam Abdulrahman Bin Faisal University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01823185

Collaborator

King Fahad Armed Forces Hospital (Other), Dammam Central Hospital (Other)

1,500

Enrollment

Locations

Arms

Duration (Months)

375

Patients Per Site

10.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease Myocardial Infarction Heart Disease Vascular Disease Angina Pectoris Cardiovascular Disease Ischemia Infarction Embolism Thrombosis Chest Pain	Drug: clopidogrel Drug: Ticagrelor or prasugrel	Phase 4

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 CYP2C192 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 Design

Study Type:

Interventional

Anticipated Enrollment :

1500 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Bedside Testing of the CYP2C19 Gene to Asses Effectiveness of Clopidogrel in Coronary Artery Disease Patients Treated With Percutaneous Coronary Intervention : Individualized Antiplatelet Drugs Treatment to Improve Prognosis

Study Start Date :

Mar 1, 2013

Anticipated Primary Completion Date :

Jan 1, 2016

Anticipated Study Completion Date :

Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: clopidogrel Genotyping will be carried out using Spartan genotyping System on all intervention group and those patients who do not carry the CYP2C19 allele 2 or 3 will be given clopidogrel (75 mg per day) while all patients who carry the CYP2C19 allele 2 or 3 will be prescribed 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. Other Names: Clavix
Experimental: 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.	Drug: 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. Other Names: Brilinta Prasuvas

Arm

Intervention/Treatment

Active Comparator: 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.

Drug: clopidogrel

Genotyping will be carried out using Spartan genotyping System on all intervention group and those patients who do not carry the CYP2C19 allele 2 or 3 will be given clopidogrel (75 mg per day) while all patients who carry the CYP2C19 allele 2 or 3 will be prescribed 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.

Other Names:

Clavix

Experimental: 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.

Drug: 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.

Other Names:

Brilinta

Prasuvas

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Prince Sultan Cardiac center	Al-Hasa	Saudi Arabia	31982
2	King Fahd University Hospital	Al-Khobar	Saudi Arabia	31441
3	Saud Al-Babtain Cardiac Center	Dammam	Saudi Arabia	31463
4	King Fahd Military Medical Complex	Dammam	Saudi Arabia	31932

Sponsors and Collaborators

Imam Abdulrahman Bin Faisal University
King Fahad Armed Forces Hospital
Dammam Central Hospital

Investigators

Principal Investigator: Abdullah M Al-Rubaish, MD, Imam Abdulrahman Bin Faisal University
Study Director: Amein K Al-Ali, PhD, Imam Abdulrahman Bin Faisal University