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

NCT01505790 | Completed Phase 3

• 2 other identifiers: 2010-020095-322009-39
• Study Type: interventional
• Target: 187
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Coronary Syndromes

Outcome Measures

Primary Outcomes (1)

• the biological efficacy of tailored clopidogrel therapy

  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.

  12 months

Secondary Outcomes (2)

• clinical efficacy

  12 MONTHS

• Tolerability

  12 MONTHS

Study Arms (2)

CLOPIDOGREL GROUP

EXPERIMENTAL

Drug: Clopidogrel

PRASUGREL GROUP

ACTIVE COMPARATOR

Drug: PRASUGREL

Interventions

PRASUGREL DRUG

60 mg the first day then 10 mg per day during one month

PRASUGREL GROUP

Clopidogrel DRUG

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.

CLOPIDOGREL GROUP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (1)

Assistance Publique Hopitaux de Marseille

Marseille, 13354, France

Location

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

Prasugrel Hydrochloride; Clopidogrel

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Ticlopidine; Thienopyridines; Pyridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• BERNARD BELAIGUES

  Assistance Publique hôpitaux de Marseille

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2011
• First Posted: January 9, 2012
• Study Start: July 1, 2011
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: May 23, 2012

Record last verified: 2012-05

Locations

FR (1)