Effect of Diabetes and Hepatic Enzymes Mutation on Clopidogrel VS Ticagrelor Activity in Myocardial Infarction (MI) Patients Undergoing Primary Percutaneous Coronary Intervention (PCI)

Combined Effect of Diabetes and cyp2c19 Polymorphism on Clopidogrel VS Ticagrelor Antiplatelet Activity in Patients of Anterior ST Elevation Myocardial Infarction Undergoing Primary PCI

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.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction
• Intervention / Treatment: Drug: Clopidogrel; Drug: Ticagrelor 90mg

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A blood sample of will be withdrawn from each patient to undergo genotypic testing using Real Time polymerase chain reaction (PCR) to detect polymorphism in the cyp2c19 enzyme.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

• Study Type: Observational
• Enrollment (Actual): 1022

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt, 01234567
    • faculty of pharmacy Cairo university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Clopidogrel group; Anterior myocardial infarction patients undergoing percutaneous coronary intervention take loading dose 600 mg oral clopidogrel (plavix) tablets before the procedure.	Drug: Clopidogrel; 8 tablets 75 mg clopidogrel loading dose before PCI; Other Names: plavix
Ticagrelor group; Anterior myocardial infarction patients undergoing percutaneous coronary intervention take loading dose180 mg oral ticagrelor (brilique) tablets before the procedure.	Drug: Ticagrelor 90mg; 2 tablets 90 mg brilique before PCI; Other Names: brilique

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute and sub-acute stent thrombosis	stent thrombosis 24 hr to one month after stent implantation	up to one month after stent implantation
Cardiovascular death	Death with cardiovascular etiology	three to six months after PCI
Non-fatal myocardial infarction	Survival after hospital admission due to ST elevation or non-ST elevation myocardial infarction	three to six months after PCI
Ischemic or hemorrhagic stroke		three to six monthes after PCI

Collaborators and Investigators

• Sponsor: Cairo University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2017
• Primary Completion (Actual): July 28, 2018
• Study Completion (Actual): July 28, 2018

Study Registration Dates

• First Submitted: July 29, 2018
• First Submitted That Met QC Criteria: August 2, 2018
• First Posted (Actual): August 3, 2018

Study Record Updates

• Last Update Posted (Actual): January 14, 2019
• Last Update Submitted That Met QC Criteria: January 11, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Clopidogrel
• Other Study ID Numbers: pharmacology department CU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No