Platelet Inhibition With Cangrelor and Crushed Ticagrelor in STEMI
Condition: ST Segment Elevation Myocardial Infarction; Percutaneous Coronary Intervention
MeSH terms: Myocardial Infarction; ST Elevation Myocardial Infarction; Infarction
Intervention: Cangrelor; Placebo
Intervention description: Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.; Patients will be randomly assigned 1:1 to receive either cangrelor or matching placebo. The bolus will be administered at the same time of a 180 mg crushed ticagrelor loading dose and infusion will be continued for 2 h.
Intervention MeSH terms: Cangrelor
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ticagrelor; cangrelor

Summary:

      In STEMI patients undergoing PPCI there is a delayed onset of action of oral P2Y12 receptor
      inhibitors, including prasugrel and ticagrelor. Crushing prasugrel and ticagrelor improves
      their PK and PD profiles as it favors drug absorption and onset of antiplatelet effects and
      because of this, it is commonly used in STEMI patients undergoing PPCI. However, despite the
      use of crushed tablets, up to one-third of patients may still have high on-treatment platelet
      reactivity (HPR) within the first 2 hours after loading dose (LD) administration of these
      oral agents. Cangrelor is a potent intravenous P2Y12 receptor inhibitor with rapid onset and
      offset of action associated with a greater reduction in ischemic events compared with
      clopidogrel in P2Y12 receptor naïve patients undergoing PCI. To date most studies have
      explored cangrelor in the setting of PCI subjects treated with clopidogrel. The PD effects of
      cangrelor in STEMI patients undergoing PPCI treated with a newer generation P2Y12 receptor
      inhibitor and how this compares with a crushed formulation of the oral drug is unexplored.
      The aim of this prospective randomized study is to investigate the PD effects of cangrelor in
      STEMI patients undergoing PPCI treated with crushed ticagrelor.
    

Eligibility criteria:

        Inclusion criteria:

          -  Patients with STEMI undergoing primary PPCI

          -  Age > 18 years old

        Exclusion criteria:

          -  Inability to provide written informed consent

          -  Known history of prior intracranial bleeding

          -  On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel,
             ticagrelor) in the prior 10 days

          -  Known allergies to aspirin, ticagrelor or cangrelor

          -  On treatment with oral anticoagulant

          -  Treatment with glycoprotein IIb/IIIa inhibitors

          -  Fibrinolytics within 24 hours

          -  Active bleeding

          -  High risk of bleeding

          -  Known platelet count <80x106/mL

          -  Known hemoglobin <10 g/dL

          -  Intubated patients (prior to randomization)

          -  Known creatinine clearance <30 mL/minute or on hemodialysis.

          -  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 or lactating females.