Tailored Antiplatelet Therapy Versus Recommended Dose of Prasugrel (ANTARCTIC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Collaborators:
Eli Lilly and Company
Daiichi Sankyo Inc.
Allies in Cardiovascular Trials Initiatives and Organized Networks:ACTION
Accumetrics, Inc.
Stentys
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01538446
First received: February 20, 2012
Last updated: January 17, 2014
Last verified: November 2013

February 20, 2012
January 17, 2014
March 2012
September 2015   (final data collection date for primary outcome measure)
Composite of Cardiovascular death, myocardial infarction, stroke, urgent revascularisation, stent thrombosis and bleedings according to the BARC definitions (type 2, 3 or 5) [ Time Frame: 12 months after randomization ] [ Designated as safety issue: Yes ]
Composite of Cardiovascular death, myocardial infarction, stroke, urgent revascularisation, stent thrombosis and bleedings according to the BARC definitions (type 2, 3 or 5) at 12 months
Same as current
Complete list of historical versions of study NCT01538446 on ClinicalTrials.gov Archive Site
  • Evaluation of the benefice of prasugrel adjustment on the composite ischemic endpoint of cardiovascular (CV) death, MI, definite stent thrombosis and Urgent revascularisation [ Time Frame: 12 months after randomization ] [ Designated as safety issue: No ]
    The key secondary objective is to evaluate 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
  • CV death, MI, stroke [ Time Frame: 12 months after randomization ] [ Designated as safety issue: No ]
  • CV death, MI, stroke or Urgent Revascularization [ Time Frame: 12 months after randomization ] [ Designated as safety issue: No ]
  • CV death: any death through at 12 months [ Time Frame: 12 months after randomization ] [ Designated as safety issue: No ]
  • Any death or resuscitated cardiac death through at 12 months [ Time Frame: 12 months after randomization ] [ Designated as safety issue: No ]
  • CV death or MI [ Time Frame: 12 months after randomization ] [ Designated as safety issue: No ]
  • Definite stent thrombosis (ARC definition) [ Time Frame: 12 months after randomization ] [ Designated as safety issue: No ]
  • All types of bleeding according to the BARC definitions 1, 2, 3, 4, 5 [ Time Frame: 12 months after randomization ] [ Designated as safety issue: Yes ]
  • BARC Bleeding of type 2, 3 or 5 [ Time Frame: 12 months after randomization ] [ Designated as safety issue: Yes ]
  • Bleeding TIMI major [ Time Frame: 12 months after randomization ] [ Designated as safety issue: Yes ]
  • GUSTO severe or moderate bleeding [ Time Frame: 12 months after randomization ] [ Designated as safety issue: Yes ]
  • STEEPLE bleeding definitions (major, minor or both) [ Time Frame: 12 months after randomization ] [ Designated as safety issue: Yes ]
  • ISTH bleeding definitions (major and clinically relevant non major) [ Time Frame: 12 months after randomization ] [ Designated as safety issue: Yes ]
  • Bleeding TIMI minor [ Time Frame: 12 months after randomization ] [ Designated as safety issue: Yes ]
  • Bleeding TIMI minimal [ Time Frame: 12 months after randomization ] [ Designated as safety issue: Yes ]
  • Bleeding TIMI major, minor and combination [ Time Frame: 12 months after randomization ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Tailored Antiplatelet Therapy Versus Recommended Dose of Prasugrel
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

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).

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: 50 French high volume PCI centers

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Acute Coronary Syndrome
  • Drug: 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)
  • Drug: prasugrel / clopidogrel
    fixed dose of prasugrel 5 mg
  • Device: 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)
  • Experimental: 1: Monitoring Arm
    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
    Interventions:
    • Drug: Modification of Prasugrel based on a biological assay
    • Device: Verify Now
  • Active Comparator: 2: Conventional Arm
    Conventional Arm: fixed dose of prasugrel 5 mg
    Intervention: Drug: prasugrel / clopidogrel
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
852
September 2015
September 2015   (final data collection date for primary outcome measure)

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
Both
75 Years and older
No
Contact: Gilles MONTALESCOT, MD,PhD 0033142163007 gilles.montalescot@psl.aphp.fr
Contact: Guillaume CAYLA guillaumecayla@free.fr
France
 
NCT01538446
P110101
Yes
Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
  • Eli Lilly and Company
  • Daiichi Sankyo Inc.
  • Allies in Cardiovascular Trials Initiatives and Organized Networks:ACTION
  • Accumetrics, Inc.
  • Stentys
Principal Investigator: Gilles MONTALESCOT, MD,PhD Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP