In Vitro Pharmacodynamic Effects of Cangrelor in Ticagrelor Treated Patients

Not Applicable

Completed

• Conditions: Coronary Artery Disease
• Interventions: Drug: Ticagrelor 90mg; Drug: Ticagrelor 180mg

• Registration Number: NCT02081443
• Lead Sponsor: University of Florida

Brief 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.

Detailed 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.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2014-03-05
• Study First Submitted QC: 2014-03-06
• Study First Posted: 2014-03-07
• Study Start: 2014-04
• Primary Completion: 2015-10
• Study Completion: 2015-10
• Results First Submitted: 2017-01-12
• Results First Submitted QC: 2017-01-12
• Status Verified: 2017-03
• Results First Posted: 2017-03-03
• Last Update Submitted: 2017-03-03
• Last Update Posted: 2017-04-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ticagrelor 180mg	Ticagrelor 90mg	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. Platelet function assays will be done following in vitro incubation with and without 500 nM cangrelor.
Ticagrelor 90mg	Ticagrelor 180mg	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. Platelet function assays will be done following in vitro incubation with and without 500 nM cangrelor.

Primary Outcome Measures

Name	Time	Method
Platelet Reactivity Index (PRI) Determined by Whole Blood Vasodilator-stimulated Phosphoprotein (VASP)	Baseline	PRI determined by VASP between before and after incubation with 500 nM Cangrelor in each arm of treatment

Secondary Outcome Measures

Name	Time	Method
PRI Measured by VASP	4 hours	PRI determined by VASP between before and after incubation with 500 nM Cangrelor in each arm of treatment

Trial Locations

Locations (1)

Dominick Angiolillo; 🇺🇸 Jacksonville, Florida, United States