Pharmacodynamic and Pharmacokinetic of Switching From Cangrelor to Prasugrel in ACS Patients Undergoing PCI
Condition: Coronary Artery Disease; Acute Coronary Syndrome
MeSH terms: Coronary Artery Disease; Acute Coronary Syndrome; Syndrome
Study type: Interventional
Phase: Phase 4

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
      prasugrel is commonly utilized, there is very limited data on the optimal approach for
      switching between these therapies. The overarching aim of this investigation is to rule out a
      drug drug interaction (DDI) when cangrelor and prasugrel are concomitantly administered in
      patients undergoing coronary stenting.
    

Detailed description: 
      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
      prasugrel is commonly utilized, there is very limited data on the optimal approach for
      switching between these therapies. In particular, ruling out a drug-drug interaction (DDI) is
      critical to this extent as the presence of a DDI would translate into reduced or abolished
      antiplatelet effects exposing these acute patients to an increased thrombotic risk. There is
      an unmet need to better elucidate pharmacodynamic profiles associated with the transition
      from cangrelor to prasugrel therapy. Of note, prasugrel has recently gone off patent and the
      availability of a generic formulation will favorably impact its use. Pharmacodynamic studies
      provide some support on the safety of administering prasugrel at the start of cangrelor
      infusion. However, the available data does not allow to rule out a DDI given that there was
      no comparator arm in which prasugrel was either given alone or at the end of cangrelor
      infusion. The methodological approach for this assessment should rely on comprehensive
      pharmacodynamics investigations aimed to assess levels of P2Y12 receptor inhibition,
      pharmacokinetic 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 DDI when cangrelor and prasugrel are
      concomitantly administered in patients undergoing coronary stenting.
    

Intervention name(s): Cangrelor; Prasugrel
Intervention type(s): Drug; Drug
Intervention description(s): Cangrelor will be used at the FDA recommended dose using a 30 μg/kg bolus followed by 4 μg/kg/min infusion. The total infusion will last 2 hours.; Prasugrel will be used in line with FDA recommendations using a 60mg LD followed by a 10mg daily maintenance dose started 24 hours after LD administration
Other intervention name(s): Kengreal; Effient
Intervention MeSH terms: Prasugrel Hydrochloride; Cangrelor
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment