Clinical trial NCT03613857: Effect of Diabetes and Hepatic Enzymes Mutation on Clopidogrel VS Ticagrelor Activity in Myocardial Infarction (MI) Patients Undergoing Primary Percutaneous Coronary Intervention (PCI)
Official title: Combined Effect of Diabetes and cyp2c19 Polymorphism on Clopidogrel VS Ticagrelor Antiplatelet Activity in Patients of Anterior ST Elevation Myocardial Infarction Undergoing Primary PCI
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Myocardial Infarction
Lead sponsor: Cairo University
Sponsor class: OTHER
First posted: 2018-08-03
Enrollment: 1022
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Diabetic and non-diabetic patients with ST-elevation elevation and non-ST elevation myocardial infarction undergoing PCI.

Brief summary: In this study the combined effect of diabetes mellitus and cyp2c19 polymorphism on platelet aggregation inhibitory activity of the highest traditionally used loading dose 600 mg clopidogrel and ticagrelor 180 mg loading dose will be compared in acute coronary syndrome (ACS) patients undergoing PCI.

Detailed description: Study subjects Inclusion criteria Diabetic patients (well-controlled type 2 diabetes mellitus) and non-diabetic patients with anterior ST-elevation and non-st elevation myocardial infarction undergoing PCI.

Exclusion criteria Patients who are with a family or personal history of bleeding. Patients with platelet count less than 100 x 103/ul. Patients with known hypersensitivity to clopidogrel or ticagrelor. Patients with serious bleeding tendency, history of intracranial hemorrhage, a sign of active bleeding, uncontrolled hypertension.

Patients with severe liver disorders

Methods The study will be conducted in the cardiac intensive care unit at Assiut educational hospital of cardiovascular diseases.

* diabetic and non-diabetic patients with ST-elevation and non-ST elevation myocardial infarction undergoing PCI will be enrolled in this study.
* At baseline, all patients will undergo full clinical examination and laboratory diagnostic tests. Current and previous medical history and medication history will be thoroughly investigated.

Recruited patients will be classified into two groups. One group will receive 600 mg loading dose clopidogrel before PCI and 75 mg daily maintenance dose. The other group of patients will receive 180 mg loading dose ticagrelor before PCI and 90 mg twice daily maintenance dose.

A blood sample of will be withdrawn from each patient to undergo genotypic testing using Real Time polymerase chain reaction (PCR) to detect polymorphism in the cyp2c19 enzyme.

* Clopidogrel and ticagrelor antiplatelet activity will be assessed by estimating the maximum platelet aggregation (MPA) using light transmittance platelet aggregometry and platelet reactivity index (PRI) using whole-blood vasodilator-stimulated phosphoprotein (VASP) measured by quantitative flow cytometry.
* All patients will be followed-up for at least three to six months month by clinic visits and phone calls to detect acute and subacute stent thrombosis, acute cardiac events, revascularization and cardiovascular death after PCI.

Study endpoints Acute stent thrombosis 24 hours after PCI and sub-acute stent thrombosis within 30 days after PCI, cardiovascular death, recurrent acute cardiac events, recurrent unstable anginal pain and hospitalization for cardiovascular diseases.

Eligibility criteria: Inclusion Criteria:

-Diabetic and non-diabetic patients with anterior ST-elevation and non-ST elevation myocardial infarction undergoing PCI.

Exclusion Criteria:

* Patients who are with a family or personal history of bleeding.
* Patients with platelet count less than 100 x 103/ul.
* Patients with known hypersensitivity to clopidogrel.
* Patients with serious bleeding tendency, history of intracranial hemorrhage, signs of active bleeding, uncontrolled hypertension.
* Patients with severe liver disorders

Primary outcomes:
measure: Acute and sub-acute stent thrombosis
timeFrame: up to one month after stent implantation
measure: Cardiovascular death
timeFrame: three to six months after PCI
measure: Non-fatal myocardial infarction
timeFrame: three to six months after PCI
measure: Ischemic or hemorrhagic stroke
timeFrame: three to six monthes after PCI
Secondary outcomes:
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Faculty of pharmacy Cairo university
Study officials:
References:
citation: Mohareb MW, AbdElghany M, Zaki HF, El-Abhar HS. Diabetes and CYP2C19 Polymorphism Synergistically Impair the Antiplatelet Activity of Clopidogrel Compared With Ticagrelor in Percutaneous Coronary Intervention-treated Acute Coronary Syndrome Patients. J Cardiovasc Pharmacol. 2020 Oct;76(4):478-488. doi: 10.1097/FJC.0000000000000881.