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Trial record 90 of 459 for:    ASPIRIN AND clopidogrel AND ischemic

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

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ClinicalTrials.gov Identifier: NCT02044146
Recruitment Status : Completed
First Posted : January 23, 2014
Last Update Posted : October 5, 2018
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Derek So, Ottawa Heart Institute Research Corporation

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.


Condition or disease Intervention/treatment Phase
Acute Coronary Syndrome Percutaneous Coronary Intervention Drug: Ticagrelor, Prasugrel, Clopidogrel Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : September 2014
Actual Primary Completion Date : October 2016
Actual Study Completion Date : June 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: Ticagrelor, Prasugrel, Clopidogrel
Active Comparator: Ticagrelor
Patients will be treated with a 90mg twice daily regimen of Ticagrelor
Drug: Ticagrelor, Prasugrel, Clopidogrel
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.
Drug: Ticagrelor, Prasugrel, Clopidogrel



Primary Outcome Measures :
  1. Proportion of Patients in Therapeutic Window [ Time Frame: 1 month ]
    The primary endpoint is the proportion of patients outside of the "therapeutic window" in the personalized therapy (PN) arm compared to the ticagrelor (TG) arm at 1 month. The "therapeutic window" will be defined by platelet function values (VerifyNow P2Y12 assay - P2Y12 reaction unit (PRU) ≤ 208 (correlated with decreased ischemic outcomes) AND PRU >= 85 (correlated with decrease bleeding). This is a surrogate of NACE (net adverse clinical events)


Secondary Outcome Measures :
  1. P2Y12 Reaction Unit (PRU) [ Time Frame: Baseline, Day 1, 1 month ]
    change in PRU from baseline, day 1 to 1 month in each of the groups

  2. Bleeding [ Time Frame: 1 month, 6 months ]
    the incidence of bleeding (defined by TIMI minor and major bleeds) among groups

  3. MACE [ Time Frame: 1 month, 6 months ]
    combined clinical endpoint (MACE) including death, myocardial infarction(MI) or urgent target vessel revascularization (TVR)

  4. Stent thrombosis [ Time Frame: 1 month, 6 month ]
    stent thrombosis (ARC definite/probable)


Other Outcome Measures:
  1. Cost [ Time Frame: 1 month, 6 months ]
    Evaluate cost involved in each strategy

  2. Genetic factors associated to outcomes [ Time Frame: 1 month, 6 months ]
    Exploratory analysis of other potential genetic variants to outcomes



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02044146


Locations
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Canada, Ontario
University of Ottawa Heart Institute
Ottawa, Ontario, Canada, K1Y4W7
Canada, Quebec
Montreal Heart Institute
Montreal, Quebec, Canada, H1T1C8
Sponsors and Collaborators
Ottawa Heart Institute Research Corporation
Canadian Institutes of Health Research (CIHR)

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Responsible Party: Derek So, Associate Professor, Ottawa Heart Institute Research Corporation
ClinicalTrials.gov Identifier: NCT02044146     History of Changes
Other Study ID Numbers: 20130601
First Posted: January 23, 2014    Key Record Dates
Last Update Posted: October 5, 2018
Last Verified: October 2018

Additional relevant MeSH terms:
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Myocardial Ischemia
Clopidogrel
Syndrome
Acute Coronary Syndrome
Disease
Pathologic Processes
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Ticagrelor
Prasugrel Hydrochloride
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs