A Pragmatic Randomized Trial to Evaluate the Comparative Effectiveness Between Dapagliflozin and Standard of Care in Type 2 Diabetes Patients

Study Overview
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Brief Summary
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A trial of patients with type 2 diabetes mellitus to evaluate the comparative effectiveness between dapagliflozin and Standard of Care (SOC)

Detailed Description
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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)

Official Title
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A Pragmatic Randomized Trial to Evaluate the Comparative Effectiveness Between Dapagliflozin and Standard of Care in Type 2 Diabetes Patients (DECIDE Study)

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Standard of Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For inclusion in the study patients should fulfil the following criteria at the time of screening: Provision of informed consent prior to any study specific procedures Females and males aged ≥18 years up to ≤ 75 years Diagnosed with Type 2 Diabetes Mellitus. Uncontrolled on first-line metformin treatment, defined as ≥8 weeks on maximum tolerated dose of metformin and HbA1c > 6.5%. Ability to read and write as judged by the investigator. Exclusion Criteria: Patients should not enter the study if any of the following exclusion criteria are fulfilled: Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site) Previous enrolment or randomization in the present study Age > 75 years Pregnancy/active breast feeding at the time of inclusion Known moderate to severe renal impairment (eGFR<60ml/min). Participation in an interventional clinical trial ≤ 3 months before enrolment. Unsuitable to participate on mental health grounds, as judged by the investigator. Physician decision to use, as second line treatment, insulin, a GLP1 agonist compound or a SGLT2 inhibitor different from dapagliflozin. Presence of any of the characteristics in which the products in study are contraindicated, as per current labels.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozin 10 mg<br>Patients will be randomized to receive either dapagliflozin or SOC. As this is a pragmatic trial, there will be no additional interventions (apart from collection of PROs and occurrence of hypoglycaemias) and there will be no restriction on how GPs change the randomized treatment regimen (e.g., switch or add drugs). Patients will be followed up for 2 years (+ 12 weeks = 116 weeks) after randomization, regardless of the status of medication. | Drug: Dapagliflozin<br>* 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.<br>* Other names: FORXIGA;|
| Active Comparator: Standard of Care (SOC)<br>Patients will be randomized to receive either dapagliflozin or SOC. As this is a pragmatic trial, there will be no additional interventions (apart from collection of PROs and occurrence of hypoglycaemias) and there will be no restriction on how GPs change the randomized treatment regimen (e.g., switch or add drugs). Patients will be followed up for 2 years (+ 12 weeks = 116 weeks) after randomization, regardless of the status of medication. | Drug: Standard of Care<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving clinical success as measured by a 4-item composite endpoint. | 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). | 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). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | HbA1c reduction | From randomization to 104 weeks of follow up. | 
| 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). | Weight Loss success | 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) | 
| 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). | 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). | 
| 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 ( | 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). | 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, closest 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, closet 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 | 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 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 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 health related quality of life as measured by SF35v2 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 | 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), | 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. | 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: | Proportion of patients with the following diabetic complications: Heart failure Gangrene or amputation of the leg, foot or toe Diabetic ketoacidosis Cerebrovascular disease Nonfatal myocardial infarction Blindness Neuropathy | up to 52 weeks following randomization and separately, up to 104 weeks following randomization. | 
| To assess differences between dapagliflozin and SOC in the change from baseline in systolic blood pressure (SBP) (mmHg) and diastolic blood pressure (DBP) (mmHg) | 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). | 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 | 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). | 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 | 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 | up to 52 weeks following randomization and separately, up to 104 weeks following randomization. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes mellitus, Randomised, Pragmatic, Standard of Care, Dapagliflozin, FORXIGA