A Multinational, Randomised, Double-Blind, Placebo-Controlled Trial to Evaluate the Effect of Ticagrelor twice daily on the Incidence of Cardiovascular Death, Myocardial Infarction or Stroke in Patients with Type 2 Diabetes Mellitus.

Study ID
STU 072014-069

Cancer Related
No

Healthy Volunteers
No

Study Sites

  • CTRC Outpatient
  • Clements University Hospital
  • Parkland Health & Hospital System

Contact
Darwynn Cole
214/648-7630
DARWYNN.COLE@UTSouthwestern.edu

Principal Investigator
Dharam Kumbhani, M.D.

Summary

Study design:
This is an event-driven, randomised, double blind, placebo controlled, parallel group, international multi-centre study to evaluate the effect of ticagrelor 60 mg bd vs. placebo for prevention of major CV events in patients with T2DM at high risk of CV events, but without a medical history of previous Mi or stroke. Patients will be managed consistent with local standard of care including provision of dietary and lifestyle advice according to local diabetes treatment guidelines. use of low-dose acetylsalicylic acid (aSa)/aspirinTM 75-150 mg once daily (od), is allowed if clinically indicated, as judged by the investigator.

Target patient population:
Men and women [GreaterThanorequalTo]50 years of age with T2DM at high risk of CV events, but without a medical history of previous Mi or stroke. Study medication, dosage and mode of administration Ticagrelor 60 mg bd given orally and corresponding placebo.

Duration of treatment:
The study is event-driven and 19000 randomised patients are estimated to be required in order to collect 1034 adjudicated primary endpoint events. The anticipated maximal duration of treatment with study medication for an individual patient is 48 months. However, the actual duration of the study will be based on accrual of the pre-determined number of adjudicated primary endpoint events, and therefore the study may be shorter or longer than 48 months. The expected minimum follow-up period is 18 months and the expected average follow-up period is 28 months, based on an enrolment period of 28 months.

Statistical methods:
all efficacy analyses will be based on the intention to treat (iTT) principle using the full analysis set (FaS) including only adjudicated endpoint events. For time to event variables, treatments will be compared using a Cox proportional hazards model with a factor for treatment group. The p-value, hazard ratio (HR) and 95% confidence interval will be reported. Kaplan-Meier estimates of the cumulative risk will also be presented. The family wise error rate will be controlled for the primary and secondary efficacy analyses by applying a hierarchical test sequence.

The final primary treatment comparison will be made at a significance level of 4.98%, adjusted for the planned efficacy interim analysis. assuming a true hazard ratio of 0.84 between ticagrelor and placebo, 1034 primary endpoint events will provide a power of 80%. With an annual event rate of 2.5% in the placebo treatment group, 19000 patients, randomised in a 1:1 ratio, are estimated to provide the required number of primary events after receiving
study medication for an anticipated average of 28 months.

Participant Eligibility

For inclusion in the study patients should fulfil the following criteria:

1. Provision of informed consent prior to any study specific procedures
2. Men or women >=50 years of age
3. Diagnosed with T2DM defined by ongoing glucose lowering drug treatment prescribed by a physician for treatment of T2DM since at least 6 months prior to Visit 1
4. At high risk of CV events, defined as history of percutaneous coronary intervention or coronary artery bypass graft or angiographic evidence of >= 50% lumen stenosis of at least 1 coronary artery.