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
  Purpose

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).


Condition Intervention Phase
Acute Coronary Syndrome
Drug: Modification of Prasugrel based on a biological assay
Drug: prasugrel / clopidogrel
Device: Verify Now
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 852
Study Start Date: March 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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)
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)
Active Comparator: 2: Conventional Arm
Conventional Arm: fixed dose of prasugrel 5 mg
Drug: prasugrel / clopidogrel
fixed dose of prasugrel 5 mg

Detailed 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: 50 French high volume PCI centers

  Eligibility

Ages Eligible for Study:   75 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01538446

Contacts
Contact: Gilles MONTALESCOT, MD,PhD 0033142163007 gilles.montalescot@psl.aphp.fr
Contact: Guillaume CAYLA guillaumecayla@free.fr

Locations
France
CHU Caremeau à Nimes - Service de Cardiologie Recruiting
Nimes, France, 30029
Contact: Guillaume CAYLA, MD    04 66 68 68 56    guillaumecayla@free.fr   
ACTION study group - Institut de Cardiologie- Hôpital la Pitié Salpêtrière Not yet recruiting
Paris, France, 75013
Contact: Gilles MONTALESCOT, MD,PhD    0033142163007    gilles.montalescot@psl.aphp.fr   
Contact: Guillaume CAYLA       guillaumecayla@free.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Eli Lilly and Company
Daiichi Sankyo Inc.
Allies in Cardiovascular Trials Initiatives and Organized Networks:ACTION
Accumetrics, Inc.
Stentys
Investigators
Principal Investigator: Gilles MONTALESCOT, MD,PhD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01538446     History of Changes
Other Study ID Numbers: P110101
Study First Received: February 20, 2012
Last Updated: January 17, 2014
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Elderly
Acute coronary syndrome
Percutaneous coronary intervention
Prasugrel
Platelet function test

Additional relevant MeSH terms:
Acute Coronary Syndrome
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Angina Pectoris
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Clopidogrel
Prasugrel
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 01, 2014