Type 2 Diabetes Mellitus
Conditions
Keywords
Type 2 diabetes mellitus, Randomised, Pragmatic, Standard of Care, Dapagliflozin, FORXIGA
Brief summary
A trial of patients with type 2 diabetes mellitus to evaluate the comparative effectiveness between dapagliflozin and Standard of Care (SOC)
Detailed description
A longitudinal, open labelled, pragmatic randomized 104 week multicentre trial of patients with type 2 diabetes mellitus to evaluate the comparative effectiveness between dapagliflozin and Standard of Care (SOC)
Interventions
DRUGDapagliflozin
The product in study is dapagliflozin (FORXIGA™), 10 mg film-coated tablets, and FORXIGA™ should be prescribed according to the instructions in the SmPC and current practice, including up-titration (if considered appropriate by the investigator). Dapagliflozin will be given in combination with metformin.
DRUGStandard of Care
The comparator arm consists of SOC. The SOC arm can be sulphonylurea (SU) or non-SU treatments. SU treatments will include any SU and the related insulin secretagogues repaglinide or nateglinide, each of them in combination with metformin. The non-SU treatments can be metformin and dipeptidyl peptidase 4 inhibitors (DPP-4i), or metformin and glitazones (pioglitazone) combination therapy. Other SGLT-2 inhibitors are excluded. All these treatments are approved in the UK for use in this patient population.
Sponsors
University of Liverpool
AstraZeneca
Clinical Practice Research Datalink
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
For inclusion in the study patients should fulfil the following criteria at the time of screening: 1. Provision of informed consent prior to any study specific procedures 2. Females and males aged ≥18 years up to ≤ 75 years 3. Diagnosed with Type 2 Diabetes Mellitus. 4. Uncontrolled on first-line metformin treatment, defined as ≥8 weeks on maximum tolerated dose of metformin and HbA1c \> 6.5%. 5. Ability to read and write as judged by the investigator.
Exclusion criteria
Patients should not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients achieving clinical success as measured by a 4-item composite endpoint. | Assessment of outcome measure will be made at the clinical evaluation that occurs closest to 52 weeks of follow-up (allowing a window of 12 weeks). | Proportion of patients achieving clinical success as measured by a 4-item composite endpoint including HbA1c reduction vs. baseline (≥ 0.5%), weight loss vs. baseline (≥ 2 Kg), no reported severe or documented hypoglycaemic events since randomization, and no switching from or adding to the treatment to which the patient was randomized (e.g., dapagliflozin or SOC),at the clinical evaluation that occurs closest to 52 weeks of follow-up (allowing a window of 12 weeks). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HbA1c success (HbA1c reduction vs. baseline ≥ 0.5%) at the clinical evaluation that occurs closest to 52 weeks of follow-up and separately, closest to 104 weeks of follow-up (in both cases, allowing a window of 12 weeks). | From randomization to 104 weeks of follow up. | HbA1c reduction |
| Weight loss success (weight vs. baseline ≥ 2 Kg) at the clinical evaluation that occurs closest to 52 weeks of follow-up and separately, closest to 104 weeks of follow-up (in both cases, allowing a window of 12 weeks). | closest to 52 weeks of follow-up and separately, closest to 104 weeks of follow-up (in both cases, allowing a window of 12 weeks) | Weight Loss success |
| Severe or documented hypoglycaemic events up to 52 weeks following randomization and separately, up to 104 weeks following randomization (in both cases, allowing a window of 12 weeks). | Up to 52 weeks following randomization and separately, up to 104 weeks following randomization (in both cases, allowing a window of 12 weeks). | Documented Hypoglycaemic events |
| To assess differences between dapagliflozin and SOC in the proportion of patients not switching from or adding to the treatment to which the patient was randomized ( | up to 52 weeks following randomization and separately, up to 104 weeks of follow-up (in both cases, allowing a window of 12 weeks). | Switching from or adding to the treatment to which the patient was randomized (e.g., dapagliflozin or SOC) up to 52 weeks following randomization and separately, up to 104 weeks of follow-up (in both cases, allowing a window of 12 weeks). |
| To assess differences between dapagliflozin and SOC in the change from baseline in HbA1 | HbA1c at the clinical evaluation that occurs closest to 52 weeks of follow-up and separately, closet to 104 weeks of follow-up (in both cases, allowing a window of 12 weeks). | HbA1c at the clinical evaluation that occurs closest to 52 weeks of follow-up and separately, closest to 104 weeks of follow-up (in both cases, allowing a window of 12 weeks). |
| To assess differences between dapagliflozin and SOC in the patients worry related to the risk of hypoglycaemic episodes measured b HFS-II Worry Scale at 6,12, 18 and 24 months | At 6, 12, 18 and 24 months | To assess differences between dapagliflozin and SOC in the patients worry related to the risk of hypoglycaemic episodes measured b HFS-II Worry Scale at 6,12, 18 and 24 months |
| To assess differences between dapagliflozin and SOC in the patients satisfaction with treatment as measured by the DTSQ at 6, 12, 18 and 24 months | At 6, 12, 18 and 24 months | To assess differences between dapagliflozin and SOC in the patients satisfaction with treatment as measured by the DTSQ at 6, 12, 18 and 24 months |
| To assess differences between dapagliflozin and SOC in the patients health related quality of life as measured by SF35v2 at 6, 12, 18 and 24 months | At 6, 12, 18 and 24 months | To assess differences between dapagliflozin and SOC in the patients health related quality of life, specifically physical, functioning, role functioning and vitality domains as measured by SF35v2 at 6, 12, 18 and 24 months |
| To assess differences between dapagliflozin and SOC in the proportion of patients needing antihypertensive escalation (dose up titration, switch and add-on strategies), | up to 52 weeks following randomization and separately, up to 104 weeks following randomization. | Antihypertensive initiation or escalation (dose up titration, switch and add-on strategies), up to 52 weeks following randomization and separately, up to 104 weeks following randomization. |
| To assess differences between dapagliflozin and SOC in the proportion of patients with diabetic complications: | up to 52 weeks following randomization and separately, up to 104 weeks following randomization. | Proportion of patients with the following diabetic complications: 1. Heart failure 2. Gangrene or amputation of the leg, foot or toe 3. Diabetic ketoacidosis 4. Cerebrovascular disease 5. Nonfatal myocardial infarction 6. Blindness 7. Neuropathy |
| To assess differences between dapagliflozin and SOC in the change from baseline in systolic blood pressure (SBP) (mmHg) and diastolic blood pressure (DBP) (mmHg) | Closest to 52 weeks of follow-up and separately, closest to 104 weeks of follow-up (in both cases, allowing a window of 12 weeks) | To assess differences between dapagliflozin and SOC in the change from baseline in systolic blood pressure (SBP) (mmHg) and diastolic blood pressure (DBP) (mmHg) at the clinical evaluation that occurs closest to 52 weeks of follow-up and separately, closest to 104 weeks of follow-up (in both cases, allowing a window of 12 weeks). |
| To assess differences between dapagliflozin and SOC in the change from baseline in eGFR | closest to 52 weeks of follow-up and separately, closest to 104 weeks of follow-up (in both cases, allowing a window of 12 weeks). | eGFR (ml/min) at the clinical evaluation that occurs closest to 52 weeks of follow-up and separately, closest to 104 weeks of follow-up (in both cases, allowing a window of 12 weeks). |
| To assess differences between dapagliflozin and SOC in the healthcare resource utilization up to 52 weeks following randomization and separately, up to 104 weeks following randomization | up to 52 weeks following randomization and separately, up to 104 weeks following randomization. | Hospitalizations, contacts due to hypoglycaemic events, needing insulin treatment, complications and unscheduled GP visits, up to 52 weeks following randomization and separately, up to 104 weeks following randomization |
Countries
United Kingdom
Contacts
PRINCIPAL_INVESTIGATORJohn Wilding, MBChB, DM
Universtiy of Liverpool, University Hospital, Aintree, Longmoor Lane, Liverpool, L9 7AL, UK
STUDY_DIRECTORJesús Medina, PhD
AstraZeneca
STUDY_DIRECTORSusan Beatty, MSc
Clinical Practice Research Datalink
Outcome results
None listed