NCT01626534

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

Completed Phase 3 Last updated 27 August 2014

What this trial tests

Phase 3 trial testing Clopidogrel in Acute Coronary Syndrome in 125 participants. Completed in 1 February 2014.

Timeline

1 March 2012

Primary endpoint
1 February 2014

1 February 2014

Quick facts

Lead sponsor	Assistance Publique Hopitaux De Marseille
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	125
Start date	1 March 2012
Primary completion	1 February 2014
Estimated completion	1 February 2014
Sites	1 location across France

Drugs / interventions tested

• Clopidogrel (clopidogrel) — full drug profile →
• trigagrelor — full drug profile →

Conditions studied

• Acute Coronary Syndrome — all drugs for Acute Coronary Syndrome →

Sponsor

Assistance Publique Hopitaux De Marseille — full company profile →

Who can join

Adults 18 to 75, any sex, with Acute Coronary Syndrome. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Numeration of cells(units) circulating endothéliales (CEC)
  Time frame: 12 months
  to estimate the balance between hurt and repair of the endothélial compartment

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. The developmental journey of therapies targeting purine receptors: from basic science to clinical trials.
   Han S, Suzuki-Kerr H, Vlajkovic SM, Thorne PR. · · 2022 · cited 9× · PMID 36173587 · DOI 10.1007/s11302-022-09896-w