Double Randomization of a Monitoring Adjusted Antiplatelet Treatment Versus a Common Antiplatelet Treatment for DES Implantation, and Interruption Versus Continuation of Double Antiplatelet Therapy (ARCTIC)

April 11, 2013 updated by: Assistance Publique - Hôpitaux de Paris

Double Randomization of a Monitoring Adjusted Antiplatelet Treatment Versus a Common Antiplatelet Treatment for DES Implantation, and a Interruption Versus Continuation of Double Antiplatelet Therapy, One Year After Stenting

Our first hypothesis is that dose adjustment of aspirin and clopidogrel based on biological monitoring reduces the rate of severe cardiovascular complications compared to a conventional strategy in patients scheduled for drug eluting stent implantation and followed up for one year. Our second hypothesis is that interruption of clopidogrel / Prasugrel after one year of a combined therapy of clopidogrel/Prasugrel and aspirin is associated with a higher rate of severe cardiovascular complications as compared with patients in whom aspirin and clopidogrel / Prasugrel is maintained during the subsequent 6 months of follow-up.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Participating Centers : 38 french high PCI volume (>700) centers Rationale: Clopidogrel / Prasugrel (75 mg/day), in combination with aspirin (75 mg/day), is currently the antiplatelet treatment of choice for prevention of stent thrombosis, and clinical trials have shown that, in high-risk patients, prolonged dual antiplatelet treatment is more effective than aspirin alone in preventing major cardiovascular events. However, despite the use of clopidogrel, a considerable number of patients continue to have cardiovascular events. Numerous in VITRO studies have shown that individual responsiveness to clopidogrel but also to aspirin is not uniform in all patients and is subject to inter- and intraindividual variability. The recent possibility of bedside monitoring of oral antiplatelet therapy offers the unique opportunity of tailoring antiplatelet therapy. However, the relevance of such strategy has never been evaluated in a randomized prospective adequately powered study having long term follow-up (rationale 1). Late state stent thrombosis, especially in the era of drug eluting stent and after interruption of OAT, is another important safety issue raising the questions of the modalities of interruption of dual OAT after one year according to the most recent updated recommendations. Can we switch from dual to single OAT after one year? If so, what is the ischemic hazard? (Rational 2) Our first hypothesis is that a strategy of dose adjustment of OAT based on biological monitoring reduces the rate of the combined ischemic endpoints of death, urgent revascularization, stent thrombosis and stroke as compared to a conventional strategy (local practice without monitoring) in patients scheduled for DES implantation and followed up for one year. Our second hypothesis is that interruption of clopidogrel after one year of dual OAT is associated with a higher rate of the same combined ischemic endpoints as compared with patients in whom dual OAT is maintained during the subsequent 6 months of follow-up. Objectives: 1) To demonstrate the superiority of the strategy of monitoring with dose adjustment in suboptimal responders (Monitoring Arm) as compared to a more conventional strategy (Conventional Arm) with fixed dose regimen of both oral antiplatelet agents in all patients as defined by the international guidelines to reduce the primary endpoint evaluated one year after DES implantation. 2) to demonstrate the superiority of a strategy of pursuit of a dual OAT beyond one year (Pursuit Arm) as compared to a strategy of interruption (Interruption Arm).

Duration of the participation : from 18 up to 30 months according to the time delay from study start to randomization. No participants will be excluded from the study at the exception of consent withdrawal. However, participants who have not been randomized for interruption or continuation of DAPT at the 12 month follow up visit will terminate the study

Number of patients: 2500 patients. This number was obtained for the demonstration of the superiority of the strategy of monitoring (Monitoring Arm) over the conventional strategy (Conventional Arm) to reduce the primary endpoint by 33% (relative risk reduction).

Expected results: The ARCTIC study will provide answers to two major clinical challenges. It will also give a unique opportunity to assess the prevalence and the associated risk factors of suboptimal answers to OAT, but also to improve a suboptimal biological response. Finally, the economic impact of both strategies of monitoring and of interruption will be evaluated.

Study Type

Interventional

Enrollment (Actual)

2500

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75013
        • Institut de Cardiologie- Hopital la Pitié Salpétrière

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients (≥18 years) in whom elective DES stent placement is scheduled after diagnostic angiography
  • Patients not treated by GPIIb/IIIa inhibitors prior to randomization.
  • Provided written consent for participation in the trial prior to any study-specific procedures or requirements.

Exclusion Criteria:

  • Oral anticoagulation (Vitamin K Antagonists).
  • Contraindication for aspirin and/or clopidogrel/Prasugrel or GPIIb/IIIa inhibitors or to increasing dose of clopidogrel or aspirin
  • Ongoing or recent bleeding and/or recent major surgery (<3 weeks)
  • Severe liver dysfunction
  • Thrombocytopenia (Platelet count <80000/µl).
  • IIb/IIIa inhibitors within a week prior to randomization
  • STEMI presentation
  • Patient at risk of poor compliance to the study
  • Patient not affiliated to social security
  • Pregnant women, no signed inform consent
  • Any invasive or surgical planned intervention during the year after stent placement

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1: Monitoring Arm

First randomization:

Monitoring Arm: dose adjustment of both aspirin and clopidogrel in suboptimal responders identified based on a point of care assay (VerifyNow).
Drug: Aspirin and clopidogrel / Prasugrel
modification of aspirin and clopidogrel/Prasugrel maintenance doses based on a biological assay
Device: VerifyNow
point of care assay VerifyNow (ACCUMETRICS San Diego USA)
Drug: Aspirin and clopidogrel / Prasugrel
aspirin and clopidogrel/ Prasugrel maintenance doses (according to international guidelines)
Drug: Aspirin and clopidogrel / Prasugrel
maintenance dose of clopidogrel / Prasugrel and aspirin
Active Comparator: 2: Conventional Arm

First randomization:

Conventional Arm: fixed dose regiment of both aspirin and clopidogrel in all patients following DES implantation according to international guidelines
Drug: Aspirin and clopidogrel / Prasugrel
modification of aspirin and clopidogrel/Prasugrel maintenance doses based on a biological assay
Drug: Aspirin and clopidogrel / Prasugrel
aspirin and clopidogrel/ Prasugrel maintenance doses (according to international guidelines)
Drug: Aspirin and clopidogrel / Prasugrel
maintenance dose of clopidogrel / Prasugrel and aspirin
Experimental: 3: Pursuit Arm

Second randomization after one year of follow-up:

Pursuit Arm: Pursuit of a dual oral antiplatelet therapy (aspirin and clopidogrel) beyond one year
Drug: Aspirin and clopidogrel / Prasugrel
modification of aspirin and clopidogrel/Prasugrel maintenance doses based on a biological assay
Drug: Aspirin and clopidogrel / Prasugrel
aspirin and clopidogrel/ Prasugrel maintenance doses (according to international guidelines)
Drug: Aspirin and clopidogrel / Prasugrel
maintenance dose of clopidogrel / Prasugrel and aspirin
Active Comparator: 4: Interruption Arm

Second randomization after one year of follow-up:

Interruption Arm: Interruption of clopidogrel therapy.
Drug: Aspirin
Interruption of clopidogrel / Prasugrel after one year of follow-up

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Composite endpoint of death, myocardial infarction, stroke, urgent coronary revascularization, stent thrombosis assessed at one year for the first hypothesis and between 6 up to 18 months of follow-up for the second hypothesis
Time Frame: during the study (one year in both " monitoring " and " conventional " arms and during the periode from 6 up to 18 months in the "interruption" and "pursuit" arms)
during the study (one year in both " monitoring " and " conventional " arms and during the periode from 6 up to 18 months in the "interruption" and "pursuit" arms)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Stent thrombosis and urgent coronary revascularization
Time Frame: at month 12 and month 30
  • at month 12 for the non-randomized patients at M12
  • at month 12 and month 30 for the randomized patient
at month 12 and month 30
Rate of individual event at one year follow-up in both " monitoring " and " conventional " arms but also during the period from one year up to 24 months in the " interruption " and " pursuit " arms.
Time Frame: at month 12 and month 30
  • at month 12 for the non-randomized patients at M12
  • at month 12 and month 30 for the randomized patient
at month 12 and month 30
Time delay from treatment interruption (randomization 2) to any thrombotic event (stent thrombosis, urgent revascularization, acute myocardial infarction, cardiac death) treatment interruption(randomisation 2)
Time Frame: at month 12 and month 30
  • at month 12 for the non-randomized patients at M12
  • at month 12 and month 30 for the randomized patient
at month 12 and month 30
Treatment compliance evaluated by the number of oral antiplatelet treatment in both arms and with respect to all individual events of the primary composite endpoint
Time Frame: at month 12 and month 30
  • at month 12 for the non-randomized patients at M12
  • at month 12 and month 30 for the randomized patient
at month 12 and month 30
Rate of use of GP IIb/IIIa receptor antagonists in both " monitoring " and " conventional " arms before percutaneous coronary intervention and in bail out situations and in both.
Time Frame: at month 12 and month 30
  • at month 12 for the non-randomized patients at M12
  • at month 12 and month 30 for the randomized patient
at month 12 and month 30
Rate of suboptimal responders as defined by ARU>550 for aspirin or by a % of inhibition <15% and or a PRU<235) and the average dosage of aspirin and clopidogrel (in mg) will evaluated before and after dose adjustment (J0) and after each dose adjustment
Time Frame: at month 12 and month 30
  • at month 12 for the non-randomized patients at M12
  • at month 12 and month 30 for the randomized patient
at month 12 and month 30
Net clinical benefit (death, myocardial infarction, urgent revascularization, stent thrombosis, stroke, major bleeding)
Time Frame: at month 12 and month 30
  • at month 12 for the non-randomized patients at M12
  • at month 12 and month 30 for the randomized patient
at month 12 and month 30
Medico-economic evaluations will be performed for both hypotheses. The rate of rehospitalisation and the length of stay will be used as economic indicators
Time Frame: at month 12 and month 30
  • at month 12 for the non-randomized patients at M12
  • at month 12 and month 30 for the randomized patient
at month 12 and month 30

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

Bristol-Myers Squibb
Sanofi
Institut National de la Santé Et de la Recherche Médicale, France
Boston Scientific Corporation
Medtronic
Cordis Corporation
Fondation de France
Diagnostica Stago
Allies in Cardiovascular Trials Initiatives and Organized

Investigators

  • Principal Investigator: Gilles Montalescot, PUPH, Assistance Publique - Hopitaux de Paris
  • Principal Investigator: Jean-Philippe Collet, PH, Assistance Publique - Hopitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2009

Primary Completion (Actual)

March 1, 2012

Study Completion (Actual)

January 1, 2013

Study Registration Dates

First Submitted

January 13, 2009

First Submitted That Met QC Criteria

January 21, 2009

First Posted (Estimate)

January 22, 2009

Study Record Updates

Last Update Posted (Estimate)

April 12, 2013

Last Update Submitted That Met QC Criteria

April 11, 2013

Last Verified

April 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P080403

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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