This study is being carried out to evaluate the effect of a drug called dapagliflozin when added to current treatment for type 2 diabetes on cardiovascular events.

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2013-000239-28-DE
• Date of registration: 12/06/2013
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: This study is being carried out to evaluate the effect of a drug called dapagliflozin when added to current treatment for type 2 diabetes on cardiovascular events.
• Scientific title: 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
• Date of first enrolment: 15/10/2013
• Target sample size: 17150
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000239-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, European Union, Germany, Hong Kong, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Philippines, Poland, Russian Federation, Slovakia, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States, Vietnam

Contacts

• Name: Information Center
• Affiliation: AstraZeneca

• Name: Information Center
• Affiliation: AstraZeneca

Key inclusion & exclusion 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
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:
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 <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. Patient should be excluded if either the systolic BP is elevated (> 180 mmHg) or the diastolic BPis 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 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

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:
10. HbA1c =12% or HbA1c<6.5% from the central laboratory (nb, the
proportion of subjects with an HbA1c between 6.5 % and < 7.0 % will be capped at approximately 5 % of the study)
11. AST or ALT >3x ULN or Total bilirubin >2.5 x ULN
12. CrCl < 60 ml/min (based on the Cockroft-Gault equation)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Type 2 Diabetes mellitus
MedDRA version: 20.0 Level: SOC Classification code 10027433 Term: Metabolism and nutrition disorders System Organ Class: 10027433 - Metabolism and nutrition disorders
MedDRA version: 20.0 Level: LLT Classification code 10012613 Term: Diabetes mellitus non-insulin-dependent System Organ Class: 10027433 - Metabolism and nutrition disorders

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Trade Name: Forxiga
Product Name: Dapagliflozin
Product Code: BMS-512148
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: dapagliflozin
CAS Number: 960404-48-2
Current Sponsor code: BMS-512148-05
Other descriptive name: DAPAGLIFLOZIN PROPANEDIOL MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

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.

Primary end point(s): The co-primary 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.

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
- All-cause mortality

Timepoint(s) of evaluation of this end point: This will be evaluated at the pre-specified interim analysis and when the study has been completed.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Secondary endpoints will be evaluated when the study has been completed.

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)
- All-cause mortality (time to event)

Secondary ID(s)

2013-000239-28-GB

D1693C00001

NCT01730534

Source(s) of Monetary Support

AstraZeneca AB

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 25/09/2019
• Date Completed: 16/09/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-000239-28/results