Impact of Chronic Kidney Disease on the Effects of Ticagrelor in Patients With Diabetes and Coronary Artery Disease
Summary
Patients with diabetes mellitus (DM) are at increased risk of atherothrombotic events. Importantly, DM is a key risk factor for the development of chronic kidney disease (CKD), which further enhances atherothrombotic risk. Clopidogrel is the most widely used platelet P2Y12 receptor inhibitor. However, despite its clinical benefit, patients with DM and CKD frequently experience recurrent atherothrombotic events. Ticagrelor is an oral, reversible, non-competitive P2Y12 receptor inhibitor with more potent and consistent platelet inhibition than clopidogrel. In large-scale clinical investigation, ticagrelor significantly reduced ischemic events to a greater extent than clopidogrel, a finding that was consistent also among DM patients. To date there has been no analysis on the efficacy of ticagrelor in DM patients according to CKD status. Moreover, although pharmacodynamic (PD) studies showed enhanced platelet inhibition associated with ticagrelor, it is unknown how this may be affected by CKD status. Ultimately, how PK/PD profiles of different ticagrelor dosing regimens may be affected by DM and CKD status is also unknown. The proposed study is aimed to show the impact of CKD status among patients with DM and coronary artery disease) CAD on PD and PK profiles of ticagrelor used at 2 doses (90mg bid and 60mg bid) in the setting of a prospective, randomized, cross-over trial.
Timeline
- Start
- 2016-02
- Primary completion
- 2019-11-14
- Completion
- 2020-06-17
Outcome
Missed primary endpoint
registry analysis (superiority test); CKD - Ticagrelor 90 vs Non-CKD - Ticagrelor 90; p = 0.105; Median Difference (Net) 6.4 (95% CI -1.1 to 14.3); t-test, 2 sided NCT02539160 ↗
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Ticagrelor | Small molecule | 60 mg | Oral |
| Subject | Ticagrelor | Small molecule | 90 mg | Oral |