DECLARE Dapagliflozin Effect on CardiovascuLAR Events A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Effect of Dapagliflozin 10 mg Once Daily on the Incidence of Cardiovascular Death, Myocardial Infarction or Ischemic Stroke in Patients with Type 2 Diabetes - DECLARE

Phase 1

• Conditions: Type II Diabetes mellitus; MedDRA version: 14.1Level: LLTClassification code 10012613Term: Diabetes mellitus non-insulin-dependentSystem Organ Class: 100000004861; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2013-000239-28-IT
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-05-14
• Study Completion: 2018-09-16
• Last Update Posted: 21 December 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 17160

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
- 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.
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 8575
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8575

Exclusion Criteria

1. Use of the following excluded medications:
- Current or recent (within 24 months) treatment with pioglitazone and/or use of pioglitazone for 2 years or more at any time
- 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 tachycardia <8 weeks prior to randomization. Patients with acute cardiovascular events can be enrolled in the run-in period as long as randomization does not occur within 8 weeks of the event.
3. Systolic BP >180 or diastolic BP >100 mmHg at randomization
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 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 HbA1c<6.5%
15. AST or ALT >3x 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 likely to be compliant with the study medication and protocol.
Exclusion criteria for the optional genetic research
The exclusion criteria for the optional genetic research are provided in Appendix H.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified