Overview

This trial is active, not recruiting.

Condition acute coronary syndrome
Treatments modification of prasugrel based on a biological assay, prasugrel / clopidogrel, verify now
Phase phase 4
Sponsor Assistance Publique - Hôpitaux de Paris
Collaborator Eli Lilly and Company
Start date March 2012
End date June 2016
Trial size 880 participants
Trial identifier NCT01538446, P110101

Summary

The purpose of this study is to demonstrate the superiority of a strategy of platelet monitoring (Monitoring Arm) with down-adjustment of the dose of prasugrel in high responders and up-adjustment of the dose of prasugrel in low responders as compared to a more conventional strategy of a fixed dose of 5 mg to every patient without monitoring (Conventional Arm) as measured by a reduction in the composite endpoint of, cardiovascular (CV) death, myocardial infarction (MI) , stroke, stent thrombosis (ARC definition type "definite"), urgent revascularisation or bleeding (BARC definition type 2, 3 or 5).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Monitoring Arm: dose adjustment of prasugrel with down-adjustment of the dose of prasugrel in high responders and up-adjustment of the dose of prasugrel in low responders
modification of prasugrel based on a biological assay
Monitoring with VerifyNow P2Y12, 2 weeks after initiation of 5 mg of maintenance dose of prasugrel, reduction of antiplatelet therapy if there is high on-treatment platelet inhibition (HPI) or increase in dosing if there is high on-treatment platelet reactivity (HPR) Device: VerifyNow point of care assay VerifyNow (ACCUMETRICS San Diego USA)
verify now
Monitoring with VerifyNow P2Y12, 2 weeks after initiation of 5 mg of maintenance dose of prasugrel, reduction of antiplatelet therapy if there is high on-treatment platelet inhibition (HPI) or increase in dosing if there is high on-treatment platelet reactivity (HPR) Device: VerifyNow point of care assay VerifyNow (ACCUMETRICS San Diego USA)
(Active Comparator)
Conventional Arm: fixed dose of prasugrel 5 mg
prasugrel / clopidogrel
fixed dose of prasugrel 5 mg

Primary Outcomes

Measure
Composite of Cardiovascular death, myocardial infarction, stroke, urgent revascularisation, stent thrombosis and bleedings according to the BARC definitions (type 2, 3 or 5) through 12 months of randomisation
time frame: through 12 months of randomisation

Secondary Outcomes

Measure
Evaluation of the benefice of prasugrel adjustment on the composite ischemic endpoint of cardiovascular (CV) death, MI, definite stent thrombosis and Urgent revascularisation through 12 months of randomisation
time frame: through 12 months of randomisation
CV death, MI, stroke through 12 months of randomisation
time frame: through 12 months of randomisation
CV death, MI, stroke or Urgent Revascularization through 12 months of randomisation
time frame: through 12 months of randomisation
CV death: any death
time frame: 12 months after randomization
Any death or resuscitated cardiac death
time frame: 12 months after randomization
CV death or MI
time frame: 12 months after randomization
Definite stent thrombosis (ARC definition)
time frame: 12 months after randomization
All types of bleeding according to the BARC definitions 1, 2, 3, 4, 5
time frame: 12 months after randomization
BARC Bleeding of type 2, 3 or 5
time frame: 12 months after randomization
Bleeding TIMI major through 12 months of randomisation
time frame: through 12 months of randomisation
GUSTO severe or moderate bleeding
time frame: 12 months after randomization
STEEPLE bleeding definitions (major, minor or both)
time frame: 12 months after randomization
ISTH bleeding definitions (major and clinically relevant non major)
time frame: 12 months after randomization
Bleeding TIMI minor
time frame: 12 months after randomization
Bleeding TIMI minimal
time frame: 12 months after randomization
Bleeding TIMI major, minor and combination
time frame: 12 months after randomization

Eligibility Criteria

Male or female participants at least 75 years old.

Inclusion Criteria: - Acute coronary syndrome (STEMI and NSTEMI) treated by PCI - Stent (bare metal stent or drug eluting stent) regardless of the regime of thienopyridines administered before randomisation - Age ≥ 75 years. - Aspirin dose of 75 mg will be recommended but study authorizes doses ranging from 75-160 mg - Ability to understand and to comply with the study protocol. - Written informed consent Exclusion Criteria: - Prior history of ischemic or hemorrhagic stroke or transient ischemic attack, or sub-arachnoids haemorrhage - Have received fibrinolytic therapy within 48 hours of entry or randomisation into the study - Are receiving vitamin K antagonist - Concomitant medical illness (terminal malignancy) that is associated with reduced survival over the expected study treatment period. - History of intolerance or allergy to ASA or approved thienopyridines (ticlopidine, clopidogrel, or prasugrel) - Have active pathological bleeding or history of bleeding diathesis - Thrombocytopenia < 100 000 µL - Severe hepatic impairment (Child Pugh class C). - Have a condition associated with poor treatment compliance, including dementia or mental illness

Additional Information

Official title The ANTARCTIC Study - Assessment of a Normal Versus Tailored Dose of Prasugrel After Stenting in Patients Aged > 75 Years to Reduce the Composite of Bleeding, Stent Thrombosis and Ischemic Complications
Principal investigator Gilles MONTALESCOT, MD,PhD
Description Objective: To demonstrate the superiority of a strategy of platelet monitoring (Monitoring Arm) with down-adjustment of the dose of prasugrel in high responders and up-adjustment of the dose of prasugrel in low responders as compared to a more conventional strategy of a fixed dose of 5 mg to every patient without monitoring (Conventional Arm).Rationale: Prasugrel 10 mg is superior to clopidogrel in patients with acute coronary syndrome treated by percutaneous coronary intervention, reducing significantly the rates of ischemic events. Elderly patients appear to be at higher risk of bleeding events and pharmacokinetic data suggests that elderly patients are exposed to a higher concentration of the active metabolite of prasugrel. A reduced dose of 5 mg of prasugrel is therefore proposed to these patients to limit the risk of bleeding. On the other hand, the elderly have also a higher ischemic risk and higher levels of platelet aggregation under treatment than younger patients and may deserve stronger protection from antiplatelet therapy. Platelet function testing appears to be of particular interest in patients at high risk of both ischemic and bleeding events like the elderly. Too intense platelet inhibition may expose the elderly patients to an excessive bleeding risk. Too low platelet inhibition may expose them to recurrent cardiovascular ischemic events. The possibility of bedside monitoring of oral antiplatelet therapy offers the opportunity of tailoring prasugrel therapy in elderly patients to optimize their risk/benefit ratio. Such strategy has never been evaluated in a randomized and adequately powered study. Population: Acute coronary syndrome (STEMI and NSTEMI) treated by PCI-stent (bare metal stent or drug eluting stent) in patients aged 75 ≥ year. Methods: Monitoring with VerifyNow P2Y12, 2 weeks after initiation of 5 mg of maintenance dose of prasugrel, reduction of antiplatelet therapy if there is high on-treatment platelet inhibition (HPI) or increase in dosing if there is high on-treatment platelet reactivity (HPR). Patients will be monitored again 2 weeks later, only if they do not meet the Verifynow P2Y12 targets at the first assessment. Primary endpoint net clinical benefit at 12 months:Composite of Cardiovascular death, myocardial infarction, stroke, urgent revascularisation, stent thrombosis and bleedings according to the BARC definitions (type 2, 3 or 5) Centers: Approximately 40 French high volume PCI centers
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by Assistance Publique - Hôpitaux de Paris.