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

Acute Coronary Syndrome Clinical Trial

— RAPID MANAGE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02044146
• Other study ID #: 20130601
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: September 2014
• Est. completion date: June 2017

Study information

• Verified date: October 2018
• Source: Ottawa Heart Institute Research Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: June 2017
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Percutaneous Coronary Intervention
• Syndrome

Intervention

Drug:
• Ticagrelor, Prasugrel, Clopidogrel

Locations

Country	Name	City	State
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	University of Ottawa Heart Institute	Ottawa	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Ottawa Heart Institute Research Corporation	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cost	Evaluate cost involved in each strategy	1 month, 6 months
Other	Genetic factors associated to outcomes	Exploratory analysis of other potential genetic variants to outcomes	1 month, 6 months
Primary	Proportion of Patients in Therapeutic Window	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)	1 month
Secondary	P2Y12 Reaction Unit (PRU)	change in PRU from baseline, day 1 to 1 month in each of the groups	Baseline, Day 1, 1 month
Secondary	Bleeding	the incidence of bleeding (defined by TIMI minor and major bleeds) among groups	1 month, 6 months
Secondary	MACE	combined clinical endpoint (MACE) including death, myocardial infarction(MI) or urgent target vessel revascularization (TVR)	1 month, 6 months
Secondary	Stent thrombosis	stent thrombosis (ARC definite/probable)	1 month, 6 month