A Pharmacodynamic Study of a Personalized Strategy for P2Y12 Inhibition Versus Ticagrelor in Reducing Ischemic and Bleeding Risk

NCT ID: NCT02044146

Last Updated: 2018-10-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2017-06-30

Brief Summary

In patients with heart attacks, the treatment of choice is to restore blood flow with percutaneous coronary intervention (PCI) (use of stents (metal meshes) to open blockages). After PCI, the standard drug treatment includes aspirin and clopidogrel. These medications block full function of the platelet cells, which are responsible for clotting. Despite their use, patients after PCI are at risk for heart attacks, sudden clotting of stents or death. A major contributor may be resistance to clopidogrel. New more potent drugs, which can overcome the resistance, are now available; however, they come with an increase chance of severe bleeding and costs. An ideal solution would be to identify at-risk patients and selectively treat them with more potent drugs, while lower-risk patients continue with clopidogrel. This type of strategy (personalized strategy) would decrease heart attacks and death (compared to clopidogrel), while also preventing bleeding complications (compared to treating all patients with the new drugs).

Of resistant patients, many carry genes (inherited units) that prevent proper absorption of clopidogrel. Our group has developed and tested a new bedside genetic test, which identifies carriers of at-risk genes. However, this technique alone does not identify all at-risk patients. Consequently, we have now devised a novel tool, which combines genetics with patient characteristics to identify high-risk patients.

The present study combines this new tool into a strategy for personalized treatment. Patients with heart attacks who undergo PCI will be randomly assigned to 1 of 3 strategies: a) new personalized strategy, b) clopidogrel strategy (previous standard drug) or c) ticagrelor strategy (stronger approved drug). The function of the platelet cells will be measured at 1 month to determine potential benefits. Evaluation of this new personalized strategy is important for improving patient outcomes after PCI. The hypothesis is that patients receiving a personalized strategy will have decrease risk for future heart attacks and bleeding.

Conditions

Acute Coronary Syndrome; Percutaneous Coronary Intervention

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Personalized Therapy

A point-of-care bedside genetic test for CYP2C19\*2 and CYP2C19\*3 using a buccal swab will be conducted.2 P2Y12 inhibitory drug therapy will be then be directed based on a risk algorithm (integrating genotyping and clinical variables). Patients with "high ischemic risk" are defined as having (\*2 or \*3) and/or diabetes and/or (having age\>65 AND BMI\>=28). "High-risk" patients will be switched to prasugrel at 10mg daily, while "low ischemic risk" patients be kept on clopidogrel 75 daily. For patients \>age 75 or wt \< 60 kg, prasugrel will be reduced to 5mg daily.

Group Type: EXPERIMENTAL

Ticagrelor, Prasugrel, Clopidogrel

Intervention Type: DRUG

Ticagrelor

Patients will be treated with a 90mg twice daily regimen of Ticagrelor

Group Type: ACTIVE_COMPARATOR

Ticagrelor, Prasugrel, Clopidogrel

Intervention Type: DRUG

Clopidogrel registry arm

A concurrent registry of patients (not randomized) who are receiving clopidogrel only (as decided by treating physician) will be followed as a comparator group.

Group Type: OTHER

Ticagrelor, Prasugrel, Clopidogrel

Intervention Type: DRUG

Interventions

Ticagrelor, Prasugrel, Clopidogrel

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients: age >18 yrs, < 75yrs

-> 60 kg ( since March 2015 age >75 and < 60 kg eligible - but prasugrel reduced to 5mg daily if randomized to personalized therapy arm)

• NSTEMI undergoing PCI will be eligible

Exclusion Criteria

• Patients will be excluded if they have: i) a contra-indication for clopidogrel or prasugrel or ticagrelor (as per monograph), ii) have an intolerance to aspirin, iii) have absolute requirement for ticagrelor or prasugrel (e.g. stent thrombosis, allergic reaction to clopidogrel), iv) requirement for anti-coagulation treatment, v) a history of stroke, TIA or intracranial hemorrhage , vi) a platelet count < 100,000/μl, vii) a known bleeding diathesis, viii) hematocrit <30% or >52%, ix) severe liver dysfunction, x) renal insufficiency (creatinine clearance < 30ml/min), xi) adjuvant therapy with a glycoprotein IIbIIIa inhibitor.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Ottawa Heart Institute Research Corporation

OTHER

Sponsor Role: lead

Responsible Party

Derek So

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Ottawa Heart Institute

Ottawa, Ontario, Canada

Montreal Heart Institute

Montreal, Quebec, Canada

Countries

Canada

Other Identifiers

20130601

Identifier Type: -

Identifier Source: org_study_id