Clinical trial NCT02044146: A Pharmacodynamic Study of a Personalized Strategy for P2Y12 Inhibition Versus Ticagrelor in Reducing Ischemic and Bleeding Risk
Official title: Reassessment of Anti-Platelet Therapy Using InDividualized Strategies - Modifying Acute CoroNary Syndrome Algorithms Based on Genetic and Demographic Evaluation: The RAPID-MANAGE Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Acute Coronary Syndrome
Percutaneous Coronary Intervention
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2014-01-23
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Proportion of Patients in Therapeutic Window
timeFrame: 1 month
Secondary outcomes:
measure: P2Y12 Reaction Unit (PRU)
timeFrame: Baseline, Day 1, 1 month
measure: Bleeding
timeFrame: 1 month, 6 months
measure: MACE
timeFrame: 1 month, 6 months
measure: Stent thrombosis
timeFrame: 1 month, 6 month
Other outcomes:
measure: Cost
timeFrame: 1 month, 6 months
measure: Genetic factors associated to outcomes
timeFrame: 1 month, 6 months
Locations:
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
Study officials:
References: