Pharmacodynamic Evaluation of Switching From Prasugrel to Ticagrelor
Condition: Coronary Artery Disease; Acute Coronary Syndrome
MeSH terms: Coronary Artery Disease; Acute Coronary Syndrome
Study type: Interventional

Summary: 
      Recently, two new oral P2Y12 antagonists have been approved for clinical use: prasugrel, a
      third generation thienopyridine, and ticagrelor, a first in class
      cyclopentyltriazolopyrimidine (CPTP). These agents have been shown to be associated with more
      potent platelet inhibitory effects compared with clopidogrel. In addition, both agents have
      shown to be superior to clopidogrel in preventing recurrent ischemic events in the setting of
      acute coronary syndromes (ACS). Understanding how to switch patients from prasugrel to
      ticagrelor is an unmet need of clinical interest. The proposed PD investigation will have a
      prospective, randomized, parallel design aimed to show that switching patients from prasugrel
      to ticagrelor provides similar levels of platelet inhibition.
    

Detailed description: 
      Dual antiplatelet therapy consisting of aspirin and a P2Y12 receptor antagonist is the
      cornerstone of treatment for secondary prevention of thrombotic events in patients with
      coronary artery disease. Recently, two new oral P2Y12 antagonists have been approved for
      clinical use: prasugrel, a third generation thienopyridine, and ticagrelor, a first in class
      cyclopentyltriazolopyrimidine (CPTP). These agents have been shown to be associated with more
      potent platelet inhibitory effects compared with clopidogrel. In addition, both agents have
      shown to be superior to clopidogrel in preventing recurrent ischemic events in the setting of
      acute coronary syndromes (ACS). Therefore, current guidelines recommend prasugrel or
      ticagrelor (as first line therapy according to European Society of Cardiology) in ACS
      patients undergoing percutaneous coronary intervention (PCI). Despite the broader indication
      for ticagrelor (also medically managed ACS) and its mortality benefit, prasugrel has a higher
      uptake than ticagrelor in the US market, likely due to its earlier approval. Further,
      implementation of prasugrel into institutional protocols, particularly for ST elevation
      myocardial infarction (STEMI) patients undergoing primary PCI, may also be a reason for the
      slow uptake of ticagrelor. However, many clinicians would indeed consider ticagrelor as the
      long-term treatment of choice for a variety of reasons. Therefore, understanding how to
      switch patients from prasugrel to ticagrelor is an unmet need of clinical interest. However,
      currently, there are no data on the pharmacodynamic (PD) effects of switching from prasugrel
      to ticagrelor. The proposed PD investigation will have a prospective, randomized, parallel
      design aimed to show that switching patients from prasugrel to ticagrelor provides similar
      levels of platelet inhibition. This study will provide insights on the PD effects of
      switching and will help clinicians to choose the most appropriate schema to avoid
      complications related to inadequate antiplatelet therapy in patients with coronary artery
      disease if switching from prasugrel to ticagrelor is desired.
    

Intervention name(s): Ticagrelor 180mg; Prasugrel 10mg; Ticagrelor 90mg
Intervention type(s): Drug; Drug; Drug
Intervention description(s): After providing written informed consent, eligible patients on maintenance prasugrel meeting inclusion and exclusion criteria will be randomized in a 1:1:1 fashion to one of the following treatment arms:
A. Ticagrelor 180 mg loading dose (two 90mg ticagrelor tablets) followed by 90 mg BID maintenance dose for 7±2 days.
B. Ticagrelor 90 mg (one 90mg ticagrelor tablet) followed by 90 mg BID maintenance dose for 7±2 days C. Prasugrel 10 mg once daily maintenance dose for 7±2 days; After providing written informed consent, eligible patients on maintenance prasugrel therapy meeting inclusion and exclusion criteria will be randomized in a 1:1:1 fashion to one of the following treatment arms:
A. Ticagrelor 180 mg loading dose (two 90mg ticagrelor tablets) followed by 90 mg BID maintenance dose for 7±2 days.
B. Ticagrelor 90 mg (one 90mg ticagrelor tablet) followed by 90 mg BID maintenance dose for 7±2 days C. Prasugrel 10 mg once daily MD for 7±2 days; After providing written informed consent, eligible patients on maintenance prasugrel therapy meeting inclusion and exclusion criteria will be randomized in a 1:1:1 fashion to one of the following treatment arms:
A. Ticagrelor 180 mg loading dose (two 90mg ticagrelor tablets) followed by 90 mg BID maintenance dose for 7±2 days.
B. Ticagrelor 90 mg (one 90mg ticagrelor tablet) followed by 90 mg BID maintenance dose for 7±2 days C. Prasugrel 10 mg once daily MD for 7±2 days
Other intervention name(s): Brilinta; Effient; Brilinta
Intervention MeSH terms: Ticagrelor; Prasugrel Hydrochloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: platelet reactivity; ticagrelor; prasugrel