In Vitro Pharmacodynamic Effects of Cangrelor in Ticagrelor Treated Patients

Coronary Artery Disease Clinical Trial

Official title: In Vitro Pharmacodynamic Effects of Cangrelor on Platelet P2Y12 Receptor Mediated Signaling in Ticagrelor Treated Patients

Status Completed

Clinical Trial Summary

Cangrelor is a potent intravenous P2Y12 receptor inhibitor with rapid onset and offset of action associated with a greater reduction in ischemic events, including stent thrombosis, in patients undergoing stent procedures who have not been pretreated with clopidogrel. In vitro investigations have shown cangrelor to be associated with more rapid, potent, and consistent platelet inhibition in patients on maintenance prasugrel therapy exposed to a re-loading dose of prasugrel. However, if cangrelor exerts similar effects in ticagrelor treated patients remain unknown. The aim of the present study is to evaluate the effects on platelet function achieved after in vitro incubation with cangrelor in patients on ticagrelor maintenance dose who receive a loading dose of ticagrelor.

Clinical Trial Description

A higher degree of platelet inhibition remains the goal in the peri-interventional period in patients undergoing percutaneous coronary interventions (PCI) as this is associated with a lower rate of adverse ischemic events. Ticagrelor and prasugrel are novel and potent generation oral P2Y12 receptor inhibitors associated with a greater reduction in ischemic events compared with clopidogrel. However, both prasugrel and ticagrelor have recently showed variability in pharmacodynamic (PD) response, particularly in patients with ST-elevation myocardial infarction (STEMI) undergoing primary PCI, exposing these patients to an increased risk of thrombotic complications. These findings support the need for intravenous agents with more rapid platelet inhibiting effects. Cangrelor is a potent intravenous P2Y12 receptor inhibitor with rapid onset and offset of action associated with a greater reduction in ischemic events, including stent thrombosis, in patients undergoing PCI who have not been pretreated with clopidogrel. In vitro PD investigations have shown cangrelor to be associated with more rapid, potent, and consistent platelet inhibition in patients on maintenance prasugrel therapy exposed to a re-loading dose of prasugrel. However, if cangrelor exerts similar effects in ticagrelor treated patients remain unknown. The aim of the present study is to evaluate the PD effects achieved after in vitro incubation with cangrelor in patients on ticagrelor maintenance dose who receive a loading dose of ticagrelor. The proposed study will have a prospective, randomized, parallel design in which patients on chronic ticagrelor therapy will be assigned to receive a reloading dose of 90 or 180 mg ticagrelor. PD assessments will be done before and after incubation with cangrelor at 3 time-points. The study hypothesis is that in vitro incubation with cangrelor will lead to incremental P2Y12 receptor blockade, the extent of which will be inversely related to dose of ticagrelor. ;

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

• NCT number: NCT02081443
• Study type: Interventional
• Source: University of Florida
• Status: Completed
• Phase: N/A
• Start date: April 2014
• Completion date: October 2015