Heart failure with reduced ejection fraction
Conditions
Interventions
Trade Name: Forxiga (Dapagliflozin)
Pharmaceutical Form: Film-coated tablet
Sponsors
Assistance Publique – Hôpitaux de Paris (AP-HP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age = 18 years - NYHA functional class II-III. - NT-proBNP > 600 pg/ml (> 400 pg/ml if hospitalized for heart failure in the previous 12 months) - Left ventricular ejection fraction = 40% measured in transthoracic echocardiography in the 6 last months - Treated by optimal medical therapy (ACE-I or angiotensin receptor blocker or sacubitril-valsartan, and betablockers, and mineralocorticoid receptor antagonist and furosemide) unless such use was contraindicated or previously associated with side-effects leading to drug discontinuation. No change in drugs dosages in the last month. - Estimated glomerular filtration rate (eGFR) = 30 ml per minute per 1.73 m2 of body-surface area (according to the Modification of Diet in Renal Disease criteria). -Able to give written informed consent -If female of childbearing potential, have a negative serum pregnancy test and agree to use a validated method of birth control -Affiliation to a social security regime Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: -Hypersensitivity to dapagliflozin or to any of the excipients -Cardiac rhythm disorder including atrial fibrillation > 60 bpm -Significant valvular heart disease > II/IV -Hospitalisation for heart failure or unplanned visit for worsening heart failure in the last 3 months -Recent (last 6 months) or planned coronary revascularization -Cardiac resynchronization in the last 6 months -Acute coronary syndrome, stroke, or transient ischemic attack in the last 2 months -Body mass-index > 40 kg / m2 -Uncontrolled type 2 diabetes (Hb1AC > 9%) or type 1 diabetes -Genetic diabetes (Maturity Onset Diabetes of the Young, MODY) -Medical history of cancer (other than basal cell carcinoma) and/or treatment for cancer in the last 5 years -Treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones in the last 6 weeks -Active infectious diseases -Hypovolemia or dehydration, severe hypokalaemia, or severe hyponatremia -Contraindication to MRI or to contrast agents used -Patient on AME (state medical aid) -Pregnant or breast-feeding female -Current participation in another interventional study or being in the exclusion period at the end of a previous study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate changes in left ventricular (LV) extracellular mass index (ECMi) measured by MRI, induced by once-daily dapagliflozin 10 mg during 6 months in patients with heart failure and reduced ejection fraction.;Secondary Objective: Describe the magnitude and relationships between changes in multiorgan (heart, liver, abdominal adipose) tissue characteristics (dense & interstitial fibrosis and fat) during dapagliflozin administration.;Primary end point(s): MRI measurement of changes in left ventricular extracellular mass index (ECMI) after a 6-month once-daily dapagliflozin 10 mg regimen;Timepoint(s) of evaluation of this end point: After 6 months of treatment with dapagliflozin (10mg once daily) - visit V4. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Myocardial endpoints: ? Morphology and Function: Left and right ventricular volumes and LV mass; Left atrial volumes; Left and right ventricular and atrial ejection fraction; Peak global longitudinal, radial and circumferential LV and left atrial (LA) strain. ? MRI Tissue analysis and metabolism: LV myocardial water content, dense and interstitial fibrosis (late gadolinium enhancement and T1 mapping indices: native T1, extra cellular volume (ECV), intracellular mass index (ICMi)), epicardial adipose tissue (EAT) and steatosis (triglyceride fraction) ? to elucidate how changes in myocardial extracellular content and improvements in cardiac contractility may be related to a metabolic switch in the heart, we will study how dapagliflozin treatment modifies relative myocardial water/fat content using H1-MR spectroscopy. ? glucose metabolism with glucose uptake analysis using 18FDG-PET-MRI. Vascular endpoints: The effects of dapagliflozin therapy on the proximal aorta will be studied using high resolution aortic MRI combined with central pressures measured non-invasively. The studied vascular parameters will be: ? ascending and descending aortic areas ? ascending and descending aortic distensibility ? aortic arch PWV. Metabolic endpoints ? Evolution of body composition in multimodality imaging: abdominal subcutaneous and visceral fat in MRI using the ATQUA method (ICAN) and liver steatosis (Dixon MRI and H1-MRS). ? Changes in fasting glucagon, ß-hydroxybutyrate, glycerol, free fatty acid (FFA) and glucose metabolism. ? Subcutaneous tissue advanced end-glycation products quantifications using AGE reader. Study of the associations between the various imaging parameters and the non invasive measurement of glycated proteins in the subcutaneous tissue will be performed. Metabolomic study ? targeted metabolomics in blood.;Timepoint(s) of evaluation of this end point: After 6 months of treatment | — |
Countries
France
Contacts
Public Contactclinical trial informations
Assistance Publique – Hôpitaux de Paris (AP-HP)
Outcome results
None listed