Safety and Effectiveness of SGLT-2 Inhibitors in Patients With Heart Failure and Diabetes (REFORM)

University of Dundee

Status and phase

Completed

Phase 4

Conditions

Diabetes

Heart Failure

Treatments

Drug: Dapagliflozin

Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT02397421

2014-002742-42

Details and patient eligibility

About

Patients with diabetes are at increased risk of developing heart failure (HF) which can lead to increased shortness of breath, reduced ability to exercise and in some cases premature death as the heart becomes less efficient at pumping blood around the body. However the treatment options for such patients remain limited.

This study will test the safety and benefits of using a new class of drug, the SGLT2 Inhibitor (Dapagliflozin), in treating HF and diabetes.

Participants will have a Magnetic Resonance Imaging (MRI) scan of the heart, to measure the efficiency and the extent of thickening of the heart muscle before they start on treatment of dapagliflozin, or placebo for one year. They will also do exercise testing on an exercise bike (if capable) and a walking test plus fill in some questionnaires on how their heart failure affects their quality of life. Participants will then continue as normal with currently prescribed medication for their diabetes and heart failure. After a year the tests will be repeated to determine if patients receiving Dapagliflozin benefited more than those who weren't on the drug.

This study is funded by the European Foundation for the Study of Diabetes (EFSD)

Full description

Men and women with diabetes have a 2-5-fold increased risk of heart failure (HF). The prevalence and incidence of HF is increasing in diabetes and mortality rates remain alarmingly high. This highlights the need for novel therapies in diabetes that will reduce HF risk and /or delay disease progression.

Drug options are currently limited as some diabetic therapies such as thiazolidinediones are contra-indicated in HF. SGLT2 inhibitors, the newest class of anti-diabetic drugs, are an exciting new approach to diabetes management that may have additional beneficial effects in diabetes and HF. SGLT2 inhibitors may have beneficial effects on adverse left ventricular (LV) remodelling that occurs in patients with diabetes and heart failure by reducing the load on the heart through its diuretic and blood pressure lowering actions.

Exercise intolerance is a cardinal symptom of patients with HF and improving insulin sensitivity has been shown to improve exercise capacity. SGLT2 inhibition has been shown to improve insulin sensitivity and to reduce weight and therefore has the potential to improve exercise capacity in HF.

This study will assess the potential beneficial effects of the oral SGLT2 inhibitor, dapagliflozin, on LV remodelling and exercise capacity in patients with diabetes and HF. The findings of this study may help to establish the utility of SGLT2 inhibitors in diabetic patients with HF and provide important clinical data on the impact of SGLT2 inhibition on LV remodelling.

Enrollment

56 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

were previously diagnosed with Type 2 Diabetes
are diagnosed with NYHA functional class I-III HF with prior echocardiographic evidence of Left Ventricular Systolic Dysfunction (LVSD) (At least mild LV systolic dysfunction on sonographer assessment or ejection fraction at 45% or less)
on furosemide 80mg daily or less, or equivalent loop diuretic
have stable HF symptoms for at least three months prior to consent
on stable therapy for HF for at least three months prior to consent
have not been hospitalised for HF for at least three months prior to consent

Exclusion criteria

severe hepatic disease
renal disease defined as Chronic Kidney Disease (CKD) class 3b or worse (i.e. estimated glomerular filtration rate (eGFR) / creatinine clearance CrCl <45ml/min)
systolic BP <95mmHg at screening visit
screening HbA1c <6.0%
unable to walk to perform cardio pulmonary exercise testing or 6MWT
malignancy (receiving active treatment) or other life threatening diseases
pregnant or lactating women
any contraindication to MRI (e.g. claustrophobia, metal implants, penetrative eye injury or exposure to metal fragments in eye requiring medical attention)
patients who have participated in any other clinical trial of an investigational medicinal product within the previous 30 days
patients who are unable to give informed consent
any other reason considered by a study physician to be inappropriate for inclusion.