cardiovasculair overlijden, myocard infarct en ischemische beroerte cardiovascular disease diabetes
Conditions
Interventions
Patients will use either dapagliflozin 10 mg or placebo once daily in addition
to their current anti-diabetic treatment for a period of maximally 6 years.
Sponsors
Astra Zeneca
Eligibility
Age
18 Years to 99 Years
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 run-in);2. Female or male aged * 40 years;3. Diagnosed with T2DM (See Appendix E for details);4. High Risk for CV event defined as having either established CV disease and/or multiple risk factors: - Established CV Disease (See Appendix E for details) 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 (see Appendix E for details) - Dyslipidemia - Hypertension - Current Tobacco use;5. WOCBP must take precautions to avoid pregnancy throughout the study and for 4 weeks after intake of the last dose. - WOCBP must have a negative urine pregnancy test. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal. - WOCBP must be willing to use a medically accepted method of contraception that is considered reliable in the judgment of the Investigator.;For inclusion in the optional genetic research, patients must fulfill the criterion specified in Appendix H.
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 ( see section 6.4.8.1);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 non-melanoma 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 non-cardiovascular 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 breast-feeding patients ;10. Involvement in the planning and/or conduct of the study or other dapagliflozin studies (applies to AZ, BMS, Hadassah and Thrombolysis in Myocardial Infarction [TIMI] or representative staff and/or staff at the study site);11. Previous enrollment or randomization in the present study;12. Active participation in another clinical study with IP and/or investigational device;13. Individuals at risk for poor protocol or medication compliance during run-in period (reasonable compliance defined as 80 * 120%, unless a reason for non-compliance is judged acceptable by the Investigator). If for any reason, the Investigator believes that the patient will not tolerate or be compliant with IP or study procedures, the patient should not be randomized and considered a run-in failure.;Patients will be excluded during run-in and should not be randomized if the following are observed from laboratory or observation during enrollment and run-in assessments:;14. HbA1c *12% or HbA1c3x ULN or Total bilirubin >2.5 x ULN;16. CrCl < 60 ml/min (based on the Cockroft-Gault equation) ;17. Hematuria (confirmed by microscopy at Visit 1) with no explanation as judged by the Investigator up to randomization. If bladder cancer is identified, patients are not eligible to participate.;18. Any reason the Investigator believes the patient is not lik
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary efficacy variable is the time to first event included in the composite endpoint of CV death, MI, or ischemic stroke. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary efficacy is time to secundary event variables. | — |
Countries
Netherlands
Outcome results
None listed