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

Coronary Artery Disease Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01823185
• Other study ID #: STGUD005
• Status: Recruiting
• Phase: Phase 4
• First received: March 19, 2013
• Last updated: January 20, 2016
• Start date: March 2013
• Est. completion date: March 2016

Study information

• Verified date: January 2016
• Source: Dammam University
• Contact: Amein K Al-Ali, PhD
• Phone: +966505821693
• Email: ameinomran[@]hotmail.com
• Is FDA regulated: No
• Health authority: Saudi Arabia: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1500
• Est. completion date: March 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Angina Pectoris
• Cardiovascular Disease
• Cardiovascular Diseases
• Chest Pain
• Coronary Artery Disease
• Coronary Disease
• Embolism
• Heart Disease
• Infarction
• Ischemia
• Myocardial Infarction
• Myocardial Ischemia
• Thrombosis
• Vascular Disease
• Vascular Diseases

Intervention

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.
• 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.

Locations

Country	Name	City	State
Saudi Arabia	Prince Sultan Cardiac center	Al-Hasa
Saudi Arabia	King Fahd University Hospital	Al-Khobar
Saudi Arabia	King Fahd Military Medical Complex	Dammam
Saudi Arabia	Saud Al-Babtain Cardiac Center	Dammam

Sponsors (3)

Lead Sponsor	Collaborator
Dammam University	Dammam Central Hospital, King Fahad Armed Forces Hospital

Country where clinical trial is conducted

Saudi Arabia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	cardiovascular event	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.	1 year	Yes
Secondary	Mortality	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	30 days and 1 year	Yes