Patients with Diabetes mellitus type 2 and Heart Failure with preserved Ejection Fraction.
Conditions
Interventions
Trade Name: Forxiga 10 mg
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Dapagliflozin propanediol monohydrate
Other descriptive name: DAPAGLIFLOZIN
Concentration unit: mg milligram(s)
Concen
Sponsors
Fundación para la Innovación en Biomedicina-FIBMED
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Both female and male adults between the ages of 18 and 75. • Diagnosis of DM2 based on the established criteria: HbA1c = 6.5% (48 mmol / mol) and fasting plasma glucose = 7.0 mmol / L (=126 mg / dL) or 2-h after overload = 11.1 mmol / L ( = 200 mg / dL). • LVEF = 50%. • Diagnosis of ICFEP according to clinical criteria, with a hospital admission in the previous 6 months with demonstration of diastolic dysfunction according to the echocardiographic criteria. • Stable clinical situation (> 1 month after hospitalization due to IC decompensation). • Clinical indication of cardiac catheterization. • Signature of informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 62
Exclusion criteria
Exclusion criteria: • Previous treatment with iSGLT2. • Significant coronary disease. • Aortic or mitral valve disease = moderate (grades 3 or 4/4 for valve regurgitations) • Contraindications for dapagliflozin treatment according to the data sheet (hereditary galactose intolerance, Lapp lactase insufficiency or glucose-galactose malabsorption, moderate-severe renal failure -CrCl <60 ml / min or eGFR <60 ml / min / 1 , 73 m2-, severe hepatic insufficiency).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main aim of this study is to identify the underlying mechanisms of iSGLT2, which are associated to better outcomes in HFpEF and DM2.;Secondary Objective: 1. To evaluate the impact of iSGLT2 on the diastolic and systolic properties of LV between the group treated with iSGLT2 and placebo in patients with HFpEF DM2. 2. To evaluate the impact of iSGLT2 on myocardial remodeling between the group treated with iSGLT2 and placebo in patients with HFpEF DM2. 3. To quantify the relative contribution of the intrinsic diastolic properties of the LV and the flow patterns on filling pressures of patients with HFpEF and DM2 and their modulation under treatment with iSGLT2. 4. Identify the baseline phenotypic characteristics associated with greater benefit of iSGLT2 in patients with HFpEF. 5. To correlate myocardial remodeling patterns with the intrinsic diastolic properties of chamber VI with systolic function in patients with HFpEF. 6. Establish a pattern based on plasmatic and image biomarkers to identify, select and monitor the candidates to be treated with iSGLT2.;Primary end point(s): 1. Functional Main Objective: To compare the impact of iSGLT2 (dapagliflozin 10 mg / day) on LV diastolic properties in patients with HFpEF-DM2 in terms of the change in the LV stiffness constant (S +) at the peak of effort between the two treatment groups (baseline vs. 12 months). 2. Main Structural Objective: Comparison between the two treatment groups of change (baseline vs. 12 months) in levels of plasma deposit and cross-linking biomarkers of type I collagen.;Timepoint(s) of evaluation of this end point: Baseline vs 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Baseline vs 12 months;Secondary end point(s): 1. To evaluate the impact of iSGLT2 on the diastolic and systolic properties of LV between the group treated with iSGLT2 and placebo in patients with HFpEF DM2. 2. To evaluate the impact of iSGLT2 on myocardial remodeling between the group treated with iSGLT2 and placebo in patients with HFpEF DM2. 3. To quantify the relative contribution of the intrinsic diastolic properties of the LV and the flow patterns on filling pressures of patients with HFpEF and DM2 and their modulation under treatment with iSGLT2. 4. Identify the baseline phenotypic characteristics associated with greater benefit of iSGLT2 in patients with HFpEF. 5. To correlate myocardial remodeling patterns with the intrinsic diastolic properties of chamber VI with systolic function in patients with HFpEF. 6. Establish a pattern based on plasmatic and image biomarkers to identify, select and monitor the candidates to be treated with iSGLT2. 7. To compare the histological, molecular, biochemical and biomechanical features of the HFpEF patients with and without DM2. Histological, molecular and biochemical variables obtained by cardiac biopsy and blood biomarkers will be compared, analyzing the different components of the myocardium: cardiomyocytes, extracellular matrix, intramyocardial microvasculature and inflammation. Likewise, the biomechanical properties obtained by dynamic pressure-volume catheterization (elastic recoil, relaxation, rigidity, systolic elastance) will be analyzed. The associations of histological patterns with blood biochemical markers will be studied to validate their usefulness as noninvasive biomarkers of myocardial remodeling in patients with DM2 and HFpEF. 8. To compare the relative contribution of the intrinsic diastolic properties of the ventricular chamber (relaxation, stiffness and elastic recoil), and of the flow patterns on filling pressures of patients with HFpEF and with and without | — |
Countries
Spain
Contacts
Public ContactClinical trial
Funndación para la Innovación en Biomedicina-FIBMED
Outcome results
None listed