Evaluation of Ticagrelor Anti Platelet and Pleiotropic Effects in Patients Undergoing Percutaneous Coronary Intervention for an Acute Coronary Syndrome

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique Hopitaux De Marseille
ClinicalTrials.gov Identifier:
NCT01626534
First received: March 16, 2012
Last updated: August 27, 2014
Last verified: August 2014
  Purpose

Ticagrelor is a new P2Y12 ADP receptor antagonist. This drug demonstrated a faster onset of action and a higher potency compared to clopidogrel standard regimen. Consistently these properties were associated in the PLATO trial, and particularly in the percutaneous coronary intervention (PCI) arm of the study, with a lower incidence of thrombotic complications at one year follow-up but at a price of increased major bleedings (7,8). The major finding of the trial was a significant reduction in one year mortality in patients treated with ticagrelor. This reduction in mortality may not be related to the anti-platelet effect of the drug since another potent anti-platelet agent which was recently commercialized a did not exhibit any improvement in death compared to clopidogrel. Therefore there may be non anti platelet directed properties, or pleiotropic effects, of ticagrelor that could be involved in a reduction in mortality in acute coronary syndrome (ACS) patients. In fact together with its anti platelet properties, ticagrelor, has been shown to inhibit the uptake of adenosine by red cells, leading to an increase in adenosine plasma level and then activating the low affinity adenosine receptor thus potentially affecting the vascular homeostasis including endothelial cells. Therefore, it is hypothesis that the side effects and its benefit on mortality may be related to its interaction with adenosine metabolism. In line with this hypothesis, some adverse effects of ticagrelor (bradycardia and modulation of bronchoconstriction) are compatible with the activation of low affinity A1 or A2A adenosine receptors.

In addition the investigators have recently demonstrated that P2Y12 ADP blockade did impact the endothelial compartment during PCI (9). In fact the investigators have observed that the level of PR inhibition achieved by clopidogrel before PCI correlated with the extent of endothelial damage during PCI. More potent anti platelet drugs such as ticagrelor may thus be associated with reduced peri-procedural endothelial lesion which could further improve the clinical prognosis of patients. The investigators have previously observed that endothelial marker of lesion and regeneration could be measured in the blood post PCI (10).

Finally, in the response trial no patients in the ticagrelor arm had HTPR compared to 50% in the clopidogrel arm (7). This finding is surprising since recent data suggest that some patients still exhibit HTPR following the use of the very potent third generation thienopyridine prasugrel. This may be related to the fact that in the response trial only stable patients were included.

The investigators aimed to evaluate the anti-platelet efficacy and pleiotropic effects of ticagrelor in acute coronary syndromes patients undergoing percutaneous coronary intervention.


Condition Intervention Phase
Acute Coronary Syndrome
Drug: Clopidogrel
Drug: trigagrelor
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of Ticagrelor Anti Platelet and Pleiotropic Effects in Patients Undergoing Percutaneous Coronary Intervention for an Acute Coronary Syndrome.

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Numeration of cells(units) circulating endothéliales (CEC) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    to estimate the balance between hurt and repair of the endothélial compartment


Secondary Outcome Measures:
  • NUMERATION OF microparticles ( MP) [ Time Frame: 12 MONTHS ] [ Designated as safety issue: No ]
  • NUMERATION OF THE proparents circulating endothéliaux ( PEC) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Measure the IRP [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    after a dose of load(responsibility) of ticagrelor or clopidogrel by means of the index VASP and according to the consensual definition of RPEST.


Enrollment: 125
Study Start Date: March 2012
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: clopidogrel group Drug: Clopidogrel
600mg loading dose then 75mg/day
Experimental: tricagrelor group Drug: trigagrelor
180 mg loading dose then 90 mg Twice a day

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • acute coronary syndrome patient undergoing PCI and eligible for clopidogrel or tricagrelor therapy according to the guidelines
  • Subject of more than 18 years old
  • Subject agreeing to be followed over a period of 1 month _ Subject agreeing to participate in the research and having given its signed lit consent

Exclusion Criteria:

  • crdiac arrest
  • contra indications to antiplatelet therapy
  • a platelet count < 100g/l
  • history of bleeding diathesis and concurrent severe illness with expected survival of < 1 year month
  • age < 18 years old
  • pregnant of childbearing woman
  • inability to provide an informed consent
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01626534

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: NCT01626534     History of Changes
Other Study ID Numbers: 2011-005164-15, 2011-22
Study First Received: March 16, 2012
Last Updated: August 27, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Acute Coronary Syndrome
Syndrome
Angina Pectoris
Cardiovascular Diseases
Chest Pain
Disease
Heart Diseases
Myocardial Ischemia
Pain
Pathologic Processes
Signs and Symptoms
Vascular Diseases
Clopidogrel
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 October 22, 2014