A Study Comparing Cardiovascular Effects of Ticagrelor Versus Placebo in Patients With Type 2 Diabetes Mellitus

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare the effect of ticagrelor versus placebo in patients with Type 2 Diabetes Mellitus.

Detailed Description
-----------------
A multinational, randomised, double-blind, placebo-controlled phase IIIb 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

Official Title
-----------------
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 (THEMIS - Effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study).

Conditions
-----------------
Diabetes Mellitus, Type 2

Intervention / Treatment
-----------------
* Drug: Ticagrelor 60 mg
* Drug: Ticagrelor placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men or women ≥50 years of age with type 2 diabetes mellitus on treatment with a glucose lowering medication since at least 6 months, and either documented coronary artery occlusive disease or previous revascularization of a coronary artery. Key Exclusion Criteria: History of myocardial infarction or any stroke; planned treatment with agents inhibiting blood clotting; planned use of ASA/Aspirin at doses above 150 mg daily; planned coronary, cerebrovascular, or peripheral arterial revascularization; patients with known bleeding disorders and patients who need chronic oral anticoagulant therapy or chronic low-molecular-weight heparin; history of intracranial bleeding at any time, or a history of bleeding from the gastrointestinal tract within the last 6 months or a major surgery within the last 30 days; patients with known severe liver disease or with kidney failure requiring dialysis

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 130 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ticagrelor 60 mg<br>Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1. | Drug: Ticagrelor 60 mg<br>* Ticagrelor 60 mg bd taken orally as tablets<br>* Other names: Brilinta/Brilique;|
| Placebo Comparator: Ticagrelor placebo<br>Initially ticagrelor 90 mg or corresponding placebo was the selected dose, but reduced to ticagrelor 60 mg or corresponding placebo in Clinical Study Protocol Amendment No 1. | Drug: Ticagrelor placebo<br>* Ticagrelor placebo bd taken orally as tablets<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of Cardiovascular (CV) Death, MI or Stroke | Participants with Cardiovascular (CV) death, myocardial infarction (MI) or stroke. If no event, censoring occurs at the earliest of PACD, last endpoint assessment date and non-CV death date. | From randomisation to primary analysis censoring date (PACD). Median time in study until PACD was 40 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CV Death | Participants with Cardiovascular (CV) death. If no event, censoring occurs at the earliest of PACD, last endpoint assessment date and non-CV death date. | From randomisation to primary analysis censoring date (PACD). Median time in study until PACD was 40 months. | 
| MI | Participants with myocardial infarction. If no event, censoring occurs at the earliest of primary analysis censoring date (PACD), last endpoint assessment date and death date | From randomisation to primary analysis censoring date (PACD). Median time in study until PACD was 40 months. | 
| Ischaemic Stroke | Participants with ischaemic stroke. If no event, censoring occurs at the earliest of PACD, last endpoint assessment date and death date. | From randomisation to primary analysis censoring date (PACD). Median time in study until PACD was 40 months. | 
| All-cause Death | Participants with all-cause death. If no event, censoring occurs at the earliest of PACD and last endpoint assessment date. Includes deaths based on publically available vital status data in patients who have withdrawn consent. | From randomisation to primary analysis censoring date (PACD). Median time in study until PACD was 40 months. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diabetes, Coronary artery disease, Outcome, Prevention, Antiplatelet