Antithrombotic Effects of Ticagrelor Versus Clopidogrel
Condition: Acute Coronary Syndrome
MeSH terms: Acute Coronary Syndrome
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to determine whether treatment with ticagrelor (plus aspirin and
      bivalirudin) is more effective than treatment with clopidogrel (plus aspirin and
      bivalirudin).
    

Detailed description: 
      The HORIZONS-AMI Trial compared the effectiveness of heparin plus a glycoprotein IIb/IIIa
      inhibitor (GPI) versus bivalirudin in acute myocardial infarction (AMI) patients undergoing
      stent deployment 1. Overall the data showed benefits associated with the bivalirudin
      treatment with lower rates of all-cause mortality, cardiac mortality, re-infarction and
      non-CABG related major bleeding; However, the data seems to indicate a non-significant
      increase in acute stent thrombosis in the bivalirudin group. This observation seems to
      suggest the potential benefits of adding an antiplatelet agent to bivalirudin. A study by
      Dangas G et al found that in the HORIZONS-AMI patients, the group receiving 600 mg
      loading-dose of clopidogrel had significantly lower 30-day unadjusted rates of mortality,
      reinfarction and stent thrombosis than the 300 mg loading-dose group, without increase in
      bleeding rate. Furthermore, even though the benefits of bivalirudin were independent of the
      clopidogrel loading dose; the 600mg LD was associated with more benefits with both
      anticoagulation regimens. Similar observations have been reported in the ARMYDA-6 MI study.

      It is our hypothesis that using ticagrelor instead of clopidogrel, given its more potent and
      faster activity, would have greater antithrombotic activity and therefore may reduce the rate
      of acute stent thrombosis when administered in combination with bivalirudin + ASA in AMI
      patients. To investigate this hypothesis, we will compare the antithrombotic effects of
      ticagrelor with clopidogrel, when administered in combination with ASA and bivalirudin, in
      healthy human volunteers using a cross-over study design. The antithrombotic activity will be
      assessed pre-treatment and 2-hours and 24-hours post treatment, using methodologies including
      Badimon Perfusion chamber, VerifyNow P2Y12 assay, platelet aggregation with Multiplate
      Analyzer and Thromboelastography.
    

Intervention name(s): Ticagrelor + ASA + Bivalirudin; Clopidogrel + ASA + Bivalirudin
Intervention type(s): Drug; Drug
Intervention description(s): Single loading dose of Ticagrelor (180 mg given as two 90 mg tablets), plus single dose of ASA (one 81 mg tablet) + bivalirudin administered as 0.75 mg/kg IV bolus followed by 1.75 mg/kg/hour for 1 hour.; Single loading dose of Clopidogrel (600 mg given as two 300 mg tablets), plus single dose of ASA (one 81 mg tablet) + bivalirudin administered as 0.75 mg/kg IV bolus followed by 1.75 mg/kg/hour for 1 hour.
Other intervention name(s): Brilinta (ticagrelor; Aspirin (ASA); Angiomax (bivalirudin); Plavix (clopidogrel); Aspirin (ASA); Angiomax (bivalirudin)
Intervention MeSH terms: Aspirin; Hirudins; Bivalirudin; Clopidogrel; Ticagrelor
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Antiplatelet; ticagrelor; clopidogrel; bivalirudin; thrombosis