Platelet Reactivity in Acute Non-disabling Cerebrovascular Events
Condition: Stroke; Ischemic Attack, Transient
MeSH terms: Stroke; Ischemic Attack, Transient; Ischemia
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Ticagrelor is a reversible and direct-acting oral antagonist of the P2Y12 (Purinergic
      receptor P2Y, G-protein coupled, 12) receptor for adenosine diphosphate, which provides
      faster, greater, and more consistent P2Y12 inhibition than Clopidogrel in patients with acute
      coronary syndrome, irrespective of the genetic variants affecting Clopidogrel metabolism. It
      is still undefined whether combination therapy of Ticagrelor and Aspirin is more effective
      than Clopidogrel and aspirin for minor stroke and transient ischemic attack (TIA). The
      primary purpose of the PRINCE trial is to evaluate the anti-platelet effects of a 3-month
      regimen of ticagrelor initiated with 180 mg loading dose followed by 90 mg twice/day combined
      with aspirin 100 mg/day during first 21 days versus a 3-month regimen of clopidogrel
      initiated with 300 mg loading dose of followed by 75 mg/day combined with aspirin 100 mg/day
      during first 21 days when initiated within 24 hours of symptom onset in high-risk transient
      ischemic attack or minor stroke.
    

Detailed description: 
      The PRINCE trial is a prospective, randomized, multi-centre, open-label, active-controlled,
      blinded-endpoint trial (a PROBE design concerning clinical trial). A total of approximately
      952 patients (40years≤Age<80years) with high-risk TIA (defined as an ABCD2 score ≥ 4 or the
      stenosis of offending vessel ≥ 50%) or minor ischemic stroke (defined as an NIHSS ≤ 3), who
      can be treated within 24 hours of symptom onset will be enrolled. Patients fulfilling all of
      the inclusion criteria and none of the exclusion criteria will be randomized 1:1 into two
      groups after offering informed content: 1) one group will receive a 180 mg loading dose of
      ticagrelor on the day of randomization, followed by 90 mg twice/day ticagrelor from Day 2 to
      3 months; 2) the other group will receive a 300 mg loading dose of clopidogrel on the day of
      randomization, followed by 75 mg once/day clopidogrel from Day 2 to 3 months. Aspirin will be
      given in a total dose of 100-300 mg on the first day, followed by 100 mg once/day from Day 2
      to Day 21 in the both groups. The primary objective is to assess the anti-platelet effects of
      Ticagrelor combined with Aspirin versus Clopidogrel combined with Aspirin in Chinese patients
      with high-risk TIA and minor stroke. The study consists of six visits including the day of
      randomization, 2 hours after the first anti-platelet agents, 24 hours after the first
      anti-platelet agents, Day 7+2days, Day 21±2days and Day 90±7days. Genomic DNA of all patients
      will be collected for genotyped. And the genetic variants affecting Clopidogrel metabolism
      will be analyzed. The antiplatelet effects will be analyzed in total subjects and genetic
      variants carriers. The trial is anticipated to complete in 18 months from the first subject
      recruitment , with 952 subjects recruited from 25 centres in China. A Data and Safety
      Monitoring Board (DSMB) will regularly monitor safety during the study. The trial has been
      approved by IRB(Institutional Review Board) /EC(Ethics Committee) in Beijing Tiantan
      hospital, Capital Medical University.
    

Intervention name(s): Ticagrelor and Acetylsalicylic acid; Clopidogrel and Acetylsalicylic acid
Intervention type(s): Drug; Drug
Intervention description(s): This group will receive a 180 mg loading dose of ticagrelor on the day of randomization, followed by 90 mg twice/day ticagrelor from Day 2 to 3 months; combined with Aspirin given in a total dose of 100-300 mg on the first day, followed by 100 mg once/day from Day 2 to Day 21.; This group will receive a 300 mg loading dose of clopidogrel on the day of randomization, followed by 75 mg once/day clopidogrel from Day 2 to 3 months; combined with Aspirin given in a total dose of 100-300 mg on the first day, followed by 100 mg once/day from Day 2 to Day 21.
Other intervention name(s): BRILINTA; Aspirin; Plavix; Aspirin
Intervention MeSH terms: Aspirin; Clopidogrel; Ticagrelor
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: minor stroke; transient ischemic attack; ticagrelor; clopidogrel; dual anti-platelet therapy; platelet reactivity