Reversing Ticagrelor's Effects With Fresh Platelets
Condition: Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease
Study type: Interventional
Phase: Phase 4

Summary: 
      Acute coronary syndrome (ACS) patients treated with antiplatelet drugs who require coronary
      artery bypass grafting (CABG) surgery have to wait 5-7 days for the effects of the drugs to
      wean off. This treatment-devoid period leaves the patient vulnerable, therefore any means to
      shorten this period could be useful. The present study aims to investigate the possibility of
      reversing the antiplatelet effects of ticagrelor with the help of fresh donor platelets.
      Fresh platelets will be added to blood samples of treated patients in varying concentrations
      at specific timepoints to determine the time and amount of fresh platelets needed to
      normalize platelet reactivity in the treated samples.
    

Detailed description: 
      The current American College of Cardiology/American Heart Association (ACC/AHA) guidelines
      for ACS patients requiring CABG surgery after treatment with dual antiplatelet therapy
      recommend delaying surgery for 5-7 days after discontinuation of therapy, to allow for the
      dissipation of its antiplatelet effects. This treatment-devoid waiting period puts the ACS
      patients at risk for further cardiovascular events. Any means to shorten this vulnerable
      period would be of critical value. One possibility to speed up the recovery of the inhibited
      platelets is to administer infusions of fresh platelets. In fact, platelet transfusions are
      frequently administered to patients during surgery who had received prior antiplatelet
      therapy. However, the degree to which these transfusions restore platelet function in the
      recipient subjects' blood and the time from dosing when they are most effective are unknown.
      The timing is critical in scenarios where urgent surgery is required because infusion of
      platelets too soon after antiplatelet dosing could render them useless by the residual drug
      in circulation.

      The aim of the present study is to investigate the restoration of platelet function of
      ticagrelor-treated subjects by adding donor platelets to their blood. The study would have 2
      arms mimicking different clinical scenarios:

        1. Clinical Scenario 1 - Patient given a loading dose (LD) of ticagrelor in the emergency
           room, requires surgery: A single LD of ticagrelor (180 mg) with aspirin (325 mg) will be
           given to study subjects and platelet testing will be performed after addition of fresh
           platelets to their blood ex vivo. Donor platelets will be added at 4-, 6-, 24- and
           48-hours post-dose, to assess the time required for normalizing subject's platelet
           function after a LD of ticagrelor.

        2. Clinical Scenario 2 - Patient on maintenance dosing (MD) of ticagrelor, requires
           surgery: Subjects will receive ticagrelor (90 mg twice daily) with aspirin (81 mg once
           daily) for 3-7 days. After the last dose, platelet testing will be performed after
           addition of fresh platelets to their blood ex vivo, at 4-, 6-, 24- and 48-hours
           post-dose to assess the time required for normalizing subject's platelet function after
           daily treatment with ticagrelor.

      Platelet testing will be carried out using the following methodologies:

        1. Platelet Aggregation - VerifyNow P2Y12 assay.

        2. Platelet Aggregation - Multiplate Analyzer.
    

Intervention name(s): Ticagrelor loading dose; Aspirin loading dose; Ticagrelor maintenance dose; Aspirin maintenance dose
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Single loading dose of Ticagrelor 180 mg; Single loading dose of Aspirin 325 mg; Ticagrelor 90 mg twice daily x 7 days; Aspirin 81 mg once daily x 7 days
Other intervention name(s): Brilinta; Acetylsalicylic acid; ASA; Ticagrelor; Brilinta; Aspirin; ASA
Intervention MeSH terms: Aspirin; Ticagrelor
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Antiplatelet; Ticagrelor; Platelets; Thrombosis; Coronary artery disease