- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02397421
Safety and Effectiveness of SGLT-2 Inhibitors in Patients With Heart Failure and Diabetes (REFORM)
Research Into the Effect of SGLT2 Inhibition on Left Ventricular Remodeling in Patients With Heart Failure and Diabetes Mellitus
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)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Angus
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Dundee, Angus, United Kingdom, DD1 9SY
- Ninewells Hospital and Medical School
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Treatment
Dapagliflozin 10mg once daily
|
Sodium Glucose Linked Transporter Type 2 (SGLT-2) Inhibitor
Other Names:
|
Placebo Comparator: Control
Capsules containing microcrystalline cellulose Ph Eur overencapsulated in a hard gelatine capsule shell to match the active comparator
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Capsules containing microcrystalline cellulose Ph Eur overencapsulated in a hard gelatine capsule shell to match the active comparator
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in LV end systolic volume (absolute value and indexed for BSA) or LV end diastolic volume (absolute value and indexed for BSA)
Time Frame: 1 year
|
Cardiac MRI will be performed to determine the change in end systolic and diastolic volumes between both groups of patients
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in LV mass, LV ejection fraction, RV end diastolic volume, RV end systolic volume, RV ejection fraction, atrial dimensions and volumes, and LV remodelling index (LV mass / LVEDV)
Time Frame: 1 year
|
MRI will be performed to study the effects of the intervention on various other cardiac parameters.
|
1 year
|
Fluid status (Bioelectrical Impedence Analysis (BIA)
Time Frame: 1 year
|
Bioelectrical Impedence Analysis (BIA) will be conducted to determine the effect of the study dug on overall fluid balance
|
1 year
|
Objective functional capacity (6 Minute Walk Test (6MWT)
Time Frame: 1 year
|
6 Minute Walk Test (6MWT) will be performed to objectively determine the functional capacity of participants
|
1 year
|
Exercise capacity (Cardio-pulmonary Exercise Testing (CPET)
Time Frame: 1 year
|
Cardio-pulmonary Exercise Testing (CPET) will be performed to determine the exercise capacity of participants
|
1 year
|
Quality of life (Minnesota Living with Heart Failure and SF-36 questionnaire)
Time Frame: 1 year
|
will be conducted to determine the impact of the intervention on subjective quality of life
|
1 year
|
Cardiac and inflammatory biomarkers
Time Frame: 1 year
|
Brain natriuretic peptide (BNP) and other inflammatory & oxidative stress markers will be measured
|
1 year
|
Diuretic requirement (total diuretic requirement to maintain euvolemia)
Time Frame: 1 year
|
The total diuretic requirement to maintain euvolemia will be compared between the beginning and end of the trial
|
1 year
|
Change in degree of microalbuminuria
Time Frame: 1 year
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Urinary analysis will be performed to determine if there has been any change in the severity of microalbuminuria
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1 year
|
Quantify amount of natriuresis
Time Frame: 1 year
|
Urinary analysis will be performed to quantify the amount of sodium excretion.
|
1 year
|
The safety of dapagliflozin use in diabetic, heart failure patients with regard to worsening HF, hospitalization and death will be evaluated
Time Frame: 1 year
|
1 year
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Jagdeep Singh, MBBS, University of Dundee
Publications and helpful links
General Publications
- Kanie T, Mizuno A, Takaoka Y, Suzuki T, Yoneoka D, Nishikawa Y, Tam WWS, Morze J, Rynkiewicz A, Xin Y, Wu O, Providencia R, Kwong JS. Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis. Cochrane Database Syst Rev. 2021 Oct 25;10(10):CD013650. doi: 10.1002/14651858.CD013650.pub2.
- Singh JSS, Mordi IR, Vickneson K, Fathi A, Donnan PT, Mohan M, Choy AMJ, Gandy S, George J, Khan F, Pearson ER, Houston JG, Struthers AD, Lang CC. Dapagliflozin Versus Placebo on Left Ventricular Remodeling in Patients With Diabetes and Heart Failure: The REFORM Trial. Diabetes Care. 2020 Jun;43(6):1356-1359. doi: 10.2337/dc19-2187. Epub 2020 Apr 3.
- Singh JS, Fathi A, Vickneson K, Mordi I, Mohan M, Houston JG, Pearson ER, Struthers AD, Lang CC. Research into the effect Of SGLT2 inhibition on left ventricular remodelling in patients with heart failure and diabetes mellitus (REFORM) trial rationale and design. Cardiovasc Diabetol. 2016 Jul 15;15:97. doi: 10.1186/s12933-016-0419-0.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Heart Diseases
- Cardiovascular Diseases
- Glucose Metabolism Disorders
- Metabolic Diseases
- Endocrine System Diseases
- Pathological Conditions, Anatomical
- Heart Failure
- Diabetes Mellitus
- Ventricular Remodeling
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Sodium-Glucose Transporter 2 Inhibitors
- Dapagliflozin
Other Study ID Numbers
- 2014-002742-42
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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