Ticagrelor Versus Clopidogrel in Type 2 Diabetic Patients
Condition: Type-2 Diabetes Mellitus; Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to determine whether treatment with ticagrelor + aspirin is more
      effective than treatment with clopidogrel + aspirin in patients with type-2 diabetes. Both
      treatments will be given (separately) to all subjects as a one-time loading dose (i.e. higher
      than a normal daily dose), followed by daily dose for the next 5 to 7 days. Effectiveness of
      treatment will be measured with specialized blood tests before the loading dose, at two
      time-points after the loading dose, and once after the last daily dose.
    

Detailed description: 
      The rising prevalence of diabetes mellitus and its associated cardiovascular complications
      present a major burden to healthcare providers worldwide. Cardiovascular mortality is much
      higher among subjects with Type 2 Diabetes Mellitus (T2DM). Increased platelet reactivity is
      considered a potential link between the two diseases. Thus, given the higher blood
      thrombogenicity of T2DM with CAD, the availability of more potent antiplatelet drugs should
      be associated with improvements in the prevention of cardiovascular events in the diabetic
      populations. Ticagrelor has been shown to possess a faster onset of action and more potency
      than clopidogrel. Furthermore, the PLATO has shown that these characteristics results in a
      significant reduction in Cardiovascular events and even death as compared with Clopidogrel.

      We plan to compare the antithrombotic activity of ticagrelor versus clopidogrel in T2DM
      patients using a cross-over study design. Each participant will be randomly assigned to
      receive ticagrelor/clopidogrel + aspirin as a loading dose followed by 5-7 days of daily
      maintenance dosing. After a washout period of 1-2 weeks, each participant will receive the
      second treatment (clopidogrel/ticagrelor + aspirin) again as a loading dose followed by 5-7
      days of daily dosing. Platelet function will be tested at pre-treatment baseline, two
      post-dose time-points on the day of loading dose, and one time-point after the last
      maintenance dose on day 5-7. Platelet testing will be carried out using the following
      methodologies:

        1. Badimon Perfusion Chamber: an ex-vivo model of thrombosis that has been extensively
           utilized for evaluation of antithrombotic or prothrombotic effects under various
           pathological states. The model involves native blood perfusing over a thrombogenic
           substrate, triggering thrombus formation that can be measured by planimetry.

        2. Platelet Aggregation - Multiplate Analyzer.

        3. Platelet Aggregation - VerifyNow P2Y12 assay.

        4. Vasodilator-Stimulated Phosphoprotein (VASP).
    

Intervention name(s): Ticagrelor + Aspirin; Clopidogrel + Aspirin
Intervention type(s): Drug; Drug
Intervention description(s): Single loading doses of Ticagrelor (180 mg) and ASA (325 mg), followed by daily dosing for 5-7 days (ticagrelor 90 mg twice daily + ASA 81 mg once daily).; Single loading doses of Clopidogrel (600 mg) and ASA (325 mg), followed by daily dosing for 5-7 days (clopidogrel 75 mg + ASA 81 mg once daily).
Other intervention name(s): Brilinta (ticagrelor); Aspirin (ASA); Plavix (clopidogrel); Aspirin (ASA)
Intervention MeSH terms: Aspirin; Clopidogrel; Ticagrelor
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Antiplatelet; Ticagrelor; Clopidogrel; Thrombosis; Diabetes; Coronary Artery Disease