High Ticagrelor Loading Dose in STEMI
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      Dual antiplatelet therapy consisting of aspirin and a P2Y12 receptor antagonist is the
      cornerstone of treatment for prevention of thrombotic events in patients with acute coronary
      syndromes (ACS). 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, including cardiovascular mortality. Ticagrelor was recently approved for clinical use
      in ACS patients, at a dose of 180 mg loading dose and 90 mg twice/day maintenance dose.
      Ticagrelor is considered a first line therapy to be administered as soon as possible in ACS
      patients, including those presenting with ST-elevation myocardial infarction (STEMI)
      undergoing primary percutaneous coronary intervention (PCI). However, there are discordant
      data on the onset of its antiplatelet effects in this particular setting. In particular, 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. However, if the administration of a higher
      ticagrelor loading dose may overcome this limitation is still unknown and represents the aim
      of our study. 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. This study will
      provide insights on the pharmacodynamic effects of higher ticagrelor loading doses and will
      help clinicians choose the most appropriate treatment to avoid complications related to
      inadequate platelet inhibition in the early phase of patients with STEMI undergoing primary
      PCI.
    

Intervention name(s): Ticagrelor 180mg; Ticagrelor 270mg; Ticagrelor 360mg
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 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
Other intervention name(s): Brilinta; Brilinta; Brilinta
Intervention MeSH terms: Ticagrelor
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: platelet function; ticagrelor; STEMI