Type 2 Diabetes mellitus MedDRA version: 20.0 Level: LLT Classification code 10012613 Term: Diabetes mellitus non-insulin-dependent System Organ Class: 100000072461
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For inclusion in the study patients should fulfill the following criteria: 1. Provision of informed consent prior to any study specific procedures (including runin) 2. Female or male aged = 40 years 3. Diagnosed with T2DM 4. High Risk for CV event defined as having either established CV disease and/or multiple risk factors: Established CV Disease OR No known cardiovascular disease AND at least two cardiovascular risk factors in addition to T2DM, defined as: Age = 55 years in men and = 60 in women AND presence of at least 1 of the following additional risk factors Dyslipidemia Hypertension Current Tobacco use Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 9300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 7850
Exclusion criteria
Exclusion criteria: 1. Use of the following excluded medications: Current or recent (within 24 months) treatment with pioglitazone and/or use of pioglitazone for a total of 2 years or more during lifetime Current or recent (within 12 months) treatment with rosiglitazone Previous treatment with any SGLT2 inhibitor Any patient currently receiving chronic (>30 consecutive days) treatment with an oral steroid at a dose equivalent to oral prednisolone =10 mg (e.g., betamethasone =1.2 mg, dexamethasone =1.5 mg, hydrocortisone =40 mg) per day 2. Acute cardiovascular event[e.g., acute coronary syndrome (ACS), transient ischemic attack (TIA), stroke, any revascularization, decompensated HF, sustained ventricular tachycardia 180 or diastolic BP > 100 mmHg at randomization. Patient should be excluded if either the systolic BP is elevated (> 180 mmHg) or the diastolic BP is elevated (> 100 mmHg) on both measurements 4. Diagnosis of Type 1 diabetes mellitus, MODY, or secondary diabetes mellitus 5. History of bladder cancer or history of radiation therapy to the lower abdomen or pelvis at any time 6. History of any other malignancy within 5 years (with the exception of successfully treated nonmelanoma skin cancers) 7. Chronic cystitis and/or recurrent urinary tract infections (3 or more in the last year) 8. Any conditions that, in the opinion of the Investigator, may render the patient unable to complete the study including but not limited to cardiovascular (NYHA class IV CHF, recurrent ventricular arrhythmias) or noncardiovascular disease (e.g., active malignancy with the exception of basal cell carcinoma, cirrhosis, chronic lung disease, severe autoimmune disease) and/or a likely fatal outcome within 5 years 9. Pregnant or breastfeeding patients Patients will be excluded during runin and should not be randomized if the following are observed from laboratory or observation during enrollment and runin assessments: 10. HbA1c =12% or HbA1c3x ULN or Total bilirubin >2.5 x ULN 12. CrCl < 60 ml/min (based on the CockroftGault equation)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to determine the effect of dapagliflozin relative to placebo on cardiovascular outcome when added to current background therapy in patients with type 2 diabetes mellitus (T2DM) with either established cardiovascular disease or at least two cardiovascular risk factors.; Secondary Objective: The secondary objective is to determine whether treatment with dapagliflozin relative to placebo when added to current background therapy in patients with type 2 diabetes mellitus (T2DM) with either established cardiovascular disease or at least two cardiovascular risk factors results in a reduction of: Renal composite endpoint: Confirmed sustained =40% decrease in eGFR to eGFR <60 ml/min/1.73m2 and/or ESRD (dialysis =90 days or kidney transplantation, confirmed sustained eGFR of <15 mL/min/1.73m2) and/or renal or CV death Allcause mortality ; Primary end point(s): The coprimary outcome variables of the study are the composite endpoint of cardiovascular death, myocardial infarction, or ischemic stroke (time to first event) and the composite endpoint of hospitalization for heart failure or CV death (time to first event). All components of these composites will be adjudicated. ;Timepoint(s) of evaluation of this end point: This will be evaluated at the prespecified interim analysis and when the study has been completed. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary outcome variables include: Renal composite endpoint: Confirmed sustained =40% decrease in eGFR to eGFR <60 ml/min/1.73m2 and/or ESRD (dialysis =90 days or kidney transplantation, confirmed sustained eGFR of <15 mL/min/1.73m2) and/or renal or CV death (time to first event) Allcause mortality (time to event);Timepoint(s) of evaluation of this end point: Secondary endpoints will be evaluated when the study has been completed. | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, France, Germany, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Philippines, Poland, Romania, Russian Federation, Slovakia, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States, Vietnam
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed