Clinical trial NCT01823510
Conditions: Type-2 Diabetes Mellitus Coronary Artery Disease
Keywords: Antiplatelet Ticagrelor Clopidogrel Thrombosis Diabetes Coronary Artery Disease
Sponsor: Juan J Badimon
Start date: 2013-07-01; Completion date: 2016-05-10
Enrollment: 20 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief 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).

Arms: arm 1: Loading-dose plus daily-dosing for 5-7 days. arm 2: Loading-dose plus daily-dosing for 5-7 days.
Interventions: intervention 1: Ticagrelor + Aspirin intervention 2: Clopidogrel + Aspirin
Intervention descriptions: intervention 1: 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). intervention 2: 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).

Protocol documents: