Clinical trial NCT01823185: Bedside Testing of CYP2C19 Gene for Treatment of Patients With PCI With Antiplatelet Therapy
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Coronary Artery Disease
Myocardial Infarction
Heart Disease
Vascular Disease
Angina Pectoris
Cardiovascular Disease
Ischemia
Infarction
Embolism
Thrombosis
Chest Pain
Keywords: Clopidogrel
Ticagrelor
Prasugrel
Platelet aggregation inhibitor
Dammam University
King Fahd Hospital
Purinergic P2 receptor Antagonists
Lead sponsor: Imam Abdulrahman Bin Faisal University
Sponsor class: OTHER
Collaborators: name: King Fahad Armed Forces Hospital
name: Dammam Central Hospital
First posted: 2013-04-04
Enrollment: 1500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: cardiovascular event
timeFrame: 1 year
Secondary outcomes:
measure: Mortality
timeFrame: 30 days and 1 year
Other outcomes:
Locations:
city: Al-Hasa
country: Saudi Arabia
facility: Prince Sultan Cardiac center
city: Al-Khobar
country: Saudi Arabia
facility: King Fahd University Hospital
city: Dammam
country: Saudi Arabia
facility: Saud Al-Babtain Cardiac Center
city: Dammam
country: Saudi Arabia
facility: King Fahd Military Medical Complex
Study officials:
affiliation: Imam Abdulrahman Bin Faisal University
name: Abdullah M Al-Rubaish, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Imam Abdulrahman Bin Faisal University
name: Amein K Al-Ali, PhD
role: STUDY_DIRECTOR
References:
citation: Al-Rubaish AM, Al-Muhanna FA, Alshehri AM, Al-Mansori MA, Alali RA, Khalil RM, Al Faraidy KA, Cyrus C, Sulieman MM, Vatte C, Claassens DMF, Ten Berg JM, Asselbergs FW, Al-Ali AK. Bedside testing of CYP2C19 gene for treatment of patients with PCI with antiplatelet therapy. BMC Cardiovasc Disord. 2020 Jun 3;20(1):268. doi: 10.1186/s12872-020-01558-2.