In Vitro Pharmacodynamic Effects of Cangrelor in Ticagrelor Treated Patients
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
Study type: Interventional

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.
    

Intervention name(s): Ticagrelor 180mg; Ticagrelor 90mg
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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.
Other intervention name(s): Brilinta; Brilinta
Intervention MeSH terms: Ticagrelor
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: coronary artery disease; platelet function; ticagrelor; cangrelor