High Ticagrelor Loading Dose in STEMI
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease
Intervention: Ticagrelor 180mg; Ticagrelor 270mg; Ticagrelor 360mg
Intervention description: Rndomization to standard or high ticagrelor loading dose regimens; Randomization to standard or high loading dose regimen; Randomization to standrad or high loading dose regimen
Intervention MeSH terms: Ticagrelor
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 52.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: platelet function; ticagrelor; STEMI

Summary:

      Ticagrelor is a reversible direct acting P2Y12 antagonist, which has shown to be superior to
      clopidogrel, in adjunct to aspirin, in preventing recurrent ischemic events. Ticagrelor is
      considered a first line therapy to be administered as soon as possible in ACS patients.
      However, the pharmacodynamic effects of ticagrelor at the recommended 180mg loading dose are
      delayed in patients with STEMI undergoing primary PCI. The use of higher loading dose
      regimens of ticagrelor has therefore been advocated. The proposed investigation will have a
      prospective, randomized, parallel design in which STEMI patients undergoing primary PCI will
      be randomized to receive three different loading dose of ticagrelor (180 mg, 270 mg and 360
      mg). Pharmacodynamic testing will be performed at several time points to test our study
      hypothesis that a higher loading dose regiment will achieve more promptly enhanced platelet
      inhibitory effects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with ST-elevation myocardial infarction undergoing primary PCI.

          -  Age between 18 and 80 years old.

        Exclusion Criteria:

          -  History of prior intracranial bleeding.

          -  On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel,
             ticagrelor) in past 30 days.

          -  Known allergies to aspirin or ticagrelor.

          -  On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban).

          -  Treatment with IIb/IIIa glycoprotein inhibitors.

          -  Fibrinolytics within 24 hours

          -  Known blood dyscrasia or bleeding diathesis.

          -  Known platelet count <80x106/mL.

          -  Known hemoglobin <10 g/dL.

          -  Active bleeding.

          -  Hemodynamic instability.

          -  Known creatinine clearance <30 mL/minute.

          -  Known severe hepatic dysfunction.

          -  Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker
             protection.

          -  Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction
             with Ticagrelor): Ketoconazole, itraconazole, voriconazole, clarithromycin,
             nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and
             telithromizycin.

          -  Pregnant females*.

               -  Women of childbearing age must use reliable birth control (i.e. oral
                  contraceptives) while participating in the study.