This application covers work which will be conducted as part of a larger data enabled clinical trial
called DECIDE which has already received research ethics approval.
Dapagliflozin is a drug which has been shown to be safe and to improve diabetes management. This trial aims to test Dapagliflozin’s effectiveness and tolerability in treating diabetes when used in everyday practice.
CPRD data has been used to locate a cohort of potentially eligible patients registered in CPRD contributing practices for site selection activities. DECIDE has used the CPRD Interventional Research Service Platform (IRSP) to screen eligible patients to enrol from GP practices and 632 patients were recruited in total. Recruited patients provided consent and were randomised to receive Dapagliflozin or standard care. Patients were followed up for 104 weeks (+12 week window = 116 weeks) after randomisation through data collected in IRSP as well as the extraction of their Primary Care health records and linked secondary care data. The final trial dataset will use CPRD Primary Care data linked to HES Admitted Patient Care, HES Accident and Emergency and ONS Death Registration data to supplement the analysis of clinical outcomes.
This study will help doctors to decide whether Dapagliflozin is a suitable long-term treatment for patients with type 2 diabetes who have not been able to manage on other drugs, when used in real life practice. This study will also contribute to the development of CPRD trial management as a clinical trial system for future research in the NHS.
Aim: To assess differences between dapagliflozin and SOC in the achievement of clinical success in the treatment of Type II diabetes mellitus at 52 weeks using a 4-item composite endpoint, with HbA1c and weight measured at the clinical evaluation that occurs closest to 52 weeks of follow-up, and hypoglycaemic events and treatment changes measured from randomization to 52 weeks of follow up.
Design: DECIDE is 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). All outcomes will be collected from routinely collected data in the electronic health record (EHR) or IRSP. Hospital Episode Statistics (HES) admission data will be used to determine hypoglycaemic events and hospitalisations, HES APC and HES A&E data will be used to determine serious adverse events and hypoglycaemic events, and ONS data will be used to determine mortality.
Eligibility criteria: The study will include consenting adult (≥ 18 and ≤ 75 year old) patients with a diagnosis of type 2 diabetes mellitus, uncontrolled on first-line metformin treatment. The study will exclude patients who are pregnant / on active breast feeding at the time of inclusion, as well as those under treatment with insulin or a GLP-1 agonist compound, and those with known moderate to severe renal impairment (eGFR<60ml/min).
Logistic regression will be used to assess the impact of treatment group on binary outcome measures, adjusting for randomisation stratum and baseline variables. Analysis of covariance will be used to assess impact of treatment on patient-reported outcomes. This study will help to determine whether Dapagliflozin is a suitable long-term second line treatment for patients with type 2 diabetes when used in clinical practice.
Primary outcome (ascertained using data from CPRD primary care and from secondary care HES APC/A&E data):
Clinical success at 52 weeks, as measured by a 4-item composite endpoint including HbA1c reduction vs. baseline (≥ 0.5%), weight loss vs. baseline (≥ 2 Kg) (with HbA1c and weight measured at the clinical evaluation that occurs closest to 52 weeks of follow-up), 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) (hypoglycaemic events and treatment changes measured from randomization to 52 weeks of follow up)
Secondary outcomes (all ascertained using data from CPRD primary care unless otherwise indicated/collected via the CPRD Interventional Research Service Platform (IRSP)):
• Clinical success at 104 weeks, as measured by a 4-item composite endpoint including HbA1c reduction vs. baseline (≥ 0.5%), weight loss vs. baseline (≥ 2 Kg) (with HbA1c and weight measured at the clinical evaluation that occurs closest to 104 weeks of follow-up), 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) (hypoglycaemic events and treatment changes measured from randomization to 104 weeks of follow up)
• HbA1c success (HbA1c reduction vs. baseline ≥ 0.5%) at 52 weeks and 104 weeks (separately).
• Weight loss success (weight loss vs. baseline ≥ 2 Kg).
• Severe or documented hypoglycaemic events since randomization (ascertained using data from CPRD primary care and from secondary care HES APC/A&E data).
• Switching from or adding to the treatment to which the patient was randomized.
• HFS-II Worry scale (from IRSP).
• DTSQ (from IRSP).
• SF36v2 (from IRSP).
• HbA1c.
• Total body weight.
• Systolic blood pressure (SBP) (mmHg) and diastolic blood pressure (DBP) (mmHg).
• eGFR (ml/min).
• SAEs
• Discontinuation from study medication due to SAEs
John Wilding - Chief Investigator - University of Liverpool
Susanna Dodd - Corresponding Applicant - University of Liverpool
Rebecca Ghosh - Collaborator - CPRD
HES Accident and Emergency;HES Admitted Patient Care;ONS Death Registration Data;Practice Level Index of Multiple Deprivation