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

Acute Coronary Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01626534
• Other study ID #: 2011-005164-15
• Secondary ID: 2011-22
• Status: Completed
• Phase: Phase 3
• First received: March 16, 2012
• Last updated: August 27, 2014
• Start date: March 2012
• Est. completion date: February 2014

Study information

• Verified date: August 2014
• Source: Assistance Publique Hopitaux De Marseille
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Syndrome

Intervention

Drug:
• Clopidogrel
600mg loading dose then 75mg/day
• trigagrelor
180 mg loading dose then 90 mg Twice a day

Locations

Country	Name	City	State
France	Assistance Publique Hopitaux de Marseille	Marseille

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique Hopitaux De Marseille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Numeration of cells(units) circulating endothéliales (CEC)	to estimate the balance between hurt and repair of the endothélial compartment	12 months	No
Secondary	NUMERATION OF microparticles ( MP)		12 MONTHS	No
Secondary	NUMERATION OF THE proparents circulating endothéliaux ( PEC)		12 months	No
Secondary	Measure the IRP	after a dose of load(responsibility) of ticagrelor or clopidogrel by means of the index VASP and according to the consensual definition of RPEST.	12 months	No