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Impact of Clopidogrel Dose Adjustment According to Platelet Reactivity Monitoring in Patients With High on Treatment Platelet Reactivity Undergoing Percutaneous Coronary Intervention

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique Hopitaux De Marseille
ClinicalTrials.gov Identifier:
NCT01505790
First received: August 25, 2011
Last updated: May 22, 2012
Last verified: May 2012
  Purpose

Acute coronary syndromes are related to the development of a platelet derived thrombus on a ruptured coronary atheroma. Use of dual antiplatelet therapy aspirin-thienopyridine a significantly reduced the risk of major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI). However despite these therapeutic innovations, the rate of MACE in patients treated using PCI and particularly in those suffering of an acute coronary syndrome is around 5% in randomized trials. Within the factors associated with MACE, high on treatment platelet reactivity following clopidogrel loading dose has been identified as a key factor. In fact it is widely recognized that there is a large inter individual variability in clopidogrel responsiveness. In addition several authors have demonstrated a strong link between high on treatment platelet reactivity following clopidogrel loading dose and the occurrence of post PCI MACE. Vasodilator Phosphoprotein index measurement (VASP index) enables a reproducible, standardized and specific assessment of clopidogrel responsiveness.

The investigators previous works have demonstrated that a VASP index ≥ 50% had a high negative predictive value for post PCI MACE in patients undergoing PCI and that tailored clopidogrel loading dose in order to obtain a VASP index < 50% before PCI resulted in a reduction in the rate of post PCI MACE.

Prasugrel is a new generation thienopyridine with a faster and more powerful anti platelet effect compared to clopidogrel. It was shown to be superior to clopidogrel to reduce post PCI MACE in acute coronary syndromes. However in this randomized trial prasugrel achieved an excessive blockade of platelet reactivity responsible for a significant increase in bleeding events in some patients and an insufficient blockade in up to 325% of the remaining patients.

Therefore the investigators hypothesized that a strategy of individually tailored loading and maintenance dose of clopidogrel may be superior to prasugrel standard therapy in achieving an optimal platelet reactivity inhibition in acute coronary syndrome patients undergoing PCI.


Condition Intervention Phase
Acute Coronary Syndromes
Drug: PRASUGREL
Drug: Clopidogrel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Impact of Clopidogrel Dose Adjustment According to Platelet Reactivity Monitoring in Patients With High on Treatment Platelet Reactivity Undergoing Percutaneous Coronary Intervention

Resource links provided by NLM:


Further study details as provided by Assistance Publique Hopitaux De Marseille:

Primary Outcome Measures:
  • the biological efficacy of tailored clopidogrel therapy [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    To compare the biological efficacy of tailored clopidogrel therapy according to the VASP index and prasugrel standard therapy in acute coronary syndromes patients undergoing PCI.


Secondary Outcome Measures:
  • clinical efficacy [ Time Frame: 12 MONTHS ] [ Designated as safety issue: Yes ]
    Baseline in Systolic Blood Pressure at 6 months

  • Tolerability [ Time Frame: 12 MONTHS ] [ Designated as safety issue: Yes ]
    adverse event outcome at 6 months


Enrollment: 187
Study Start Date: July 2011
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CLOPIDOGREL GROUP Drug: Clopidogrel

600 mg clopidogrel will be administered during the first 6 to 12 hours then a measure of platelets reactivity will be done. An additional administration of clopidogrel (600 mg) could be done every 6 hours until to obtain a VASP <50%. No more than 3 * 600mg of clopidogrel will be authorized in this protocol.

Then for patient which have received more than one dose of clopidogrel 600mg , 150 mg per day of clopidogrel will be administrated, for which who have received only one dose of 600mg of clopidogrel , 75 mg per day will be administrated during one month at least.

Active Comparator: PRASUGREL GROUP Drug: PRASUGREL
60 mg the first day then 10 mg per day during one month

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject in front of benefited from a coronary angioplasty with setting-up of an endoprothese for a SCA
  • Subject agreeing to be followed over a period of 1 month
  • Subject agreeing to participate in the research and having given its signed enlightened consent

Exclusion Criteria:

  • Subject minor or of more than 75 years old

    • Subject presenting a rate of red blood cells < 4 G/l or a thrombocytopenia > 100 000 / mm3 plaques
    • unaffiliated Subject in a benefit system
    • pregnant or breast-feeding Woman: a pregnancy test will be realized in a systematic way, as well as a stake under contraception of the women old enough to procreate
    • Intolerance or allergy in the aspirin or in the clopidogrel
    • Pathology associated with a life expectancy 6-month-old subordinate according to the investigator
    • haemorrhagic Syndrome threatening the vital forecast, the intra-cranial tumor
    • Contraindication in one of the medicines of the study
    • Severe hepatocellular incapacity
    • Fibrinolyse meadow or hospital intra
    • Ceaseless ventricular arrhythmias
    • State of cardiogenic shock
    • History of cerebral vascular accident
    • Weight lower than 60 kg
  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: NCT01505790

Locations
France
Assistance Publique Hopitaux de Marseille
Marseille, France, 13354
Sponsors and Collaborators
Assistance Publique Hopitaux De Marseille
Investigators
Study Director: BERNARD BELAIGUES Assistance Publique hôpitaux de Marseille
  More Information

No publications provided

Responsible Party: Assistance Publique Hopitaux De Marseille
ClinicalTrials.gov Identifier: NCT01505790     History of Changes
Other Study ID Numbers: 2010-020095-32, 2009-39
Study First Received: August 25, 2011
Last Updated: May 22, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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

ClinicalTrials.gov processed this record on November 27, 2014