PD and PK Profiles of Switching Between Cangrelor and Ticagrelor Following Ticagrelor Pre-treatment
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease
Intervention: Cangrelor; Placebo
Intervention description: Cangrelor will be used at the FDA recommended dose using a 30 μg/kg bolus followed by 4 μg/kg/min infusion. The duration of cangrelor/placebo infusion will be 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase; Normal saline will be infused for 2 hours. After completing the first phase of the study, patients will undergo a 1-4 week wash-out period and then will cross-over to the alternative treatment in the second phase
Intervention MeSH terms: Cangrelor
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: The Switching Antiplatelet Therapy-5 (SWAP-5) study will be a prospective, randomized, double-blind, placebo controlled, cross-over PK and PD investigation
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Patients, research staff and laboratory personnel will be blinded to treatment assignments. Masking and randomization of medications (cangrelor and placebo) will be performed by our institutional research pharmacy.
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ticagrelor; cangrelor; switching

Summary:

      Cangrelor is an intravenous P2Y12 inhibitor utilized as a bridge to achieve adequate platelet
      inhibition until oral P2Y12 inhibitors achieve their full antiplatelet effects in patients
      undergoing coronary stenting. Although in this setting the potent oral P2Y12 inhibitor
      ticagrelor is commonly utilized, there is very limited data on the optimal approach for
      switching between these therapies. The methodological approach for this assessment should
      rely on comprehensive pharmacodynamics (PD) investigations aimed to assess levels of P2Y12
      receptor inhibition, pharmacokinetic (PK) investigations to assess systemic levels of the
      drug/drug metabolite, and mechanistic investigations by assessment of levels of P2Y12
      receptor gene expression. The overarching aim of this investigation is to rule out a
      drug-drug interaction when ticagrelor is administered prior to cangrelor infusion.
    

Eligibility criteria:

        Inclusion criteria:

          -  Patients with known coronary artery disease (defined as prior type I myocardial
             infarction, coronary revascularization, percutaneous or surgical, or presence of at
             least a 50% stenosis in any major epicardial vessel).

          -  Age > 18 years old

          -  On aspirin 81mg/qd for at least 1 month

        Exclusion criteria:

          -  Inability to provide written informed consent

          -  Hemodynamic instability

          -  On treatment with a P2Y12 receptor antagonist (ticlopidine, clopidogrel, prasugrel,
             ticagrelor) in past 30 days

          -  Known allergies to ticagrelor or cangrelor

          -  Considered at high risk for bleeding

          -  History of intracranial bleeding/hemorrhagic stroke

          -  On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban,
             apixaban, edoxoban) within past 30 days

          -  Known platelet count <80x106/mL

          -  Known hemoglobin <10 g/dL

          -  Active bleeding

          -  Known end stage renal disease on hemodialysis

          -  Known severe hepatic dysfunction

          -  Acute or severe bronchial asthma or upper airway obstruction.

          -  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]