Dapagliflozin for Heart failure with preserved ejection fraction

Inclusion criteria

• {"criterion_text":"- Adults of both genders ≥ 18 years"}
• {"criterion_text":"- LVEF ≥ 50%"}
• {"criterion_text":"- Diagnosis of HFpEF according to clinical criteria, with a history of hospitalization or the need for intravenous diuretic treatment in the previous 6 months, along with evidence of diastolic dysfunction based on echocardiographic criteria"}
• {"criterion_text":"- Patients with or without Type II Diabetes Mellitus"}
• {"criterion_text":"- Clinically stable condition (> 1 month after hospitalization for HF decompensation or since the last dose of intravenous diuretic treatment)"}
• {"criterion_text":"- Clinical indication for cardiac catheterization"}
• {"criterion_text":"- Clinical indication to receive de novo treatment with SGLT2 inhibitors"}
• {"criterion_text":"- Signed informed consent"}

Exclusion criteria

• {"criterion_text":"- Participation in another clinical trial within 30 days prior to the start of the current study"}
• {"criterion_text":"- Pregnant or breastfeeding women"}
• {"criterion_text":"- Prior or current treatment with SGLT2 inhibitors"}
• {"criterion_text":"- Significant coronary artery disease"}
• {"criterion_text":"- Aortic or mitral valvular disease ≥ moderate"}
• {"criterion_text":"- Contraindications for dapagliflozin treatment according to the product label (hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption; moderate-to-severe renal insufficiency - CrCl < 60 ml/min or eGFR < 60 ml/min/1.73 m² -; severe hepatic insufficiency)."}
• {"criterion_text":"- Stroke within 12 months prior to inclusion"}
• {"criterion_text":"- Respiratory impairment or the need for home oxygen therapy"}
• {"criterion_text":"- Life expectancy of less than 2 years due to any cause"}

Primary endpoints

• {"endpoint_text":"- Systolic properties derived from PV curve analysis: Maximum elastance","definition_or_measurement_approach":"Derived from pressure-volume (PV) curve analysis; maximum elastance measured from PV analysis."}
• {"endpoint_text":"- Diastolic properties derived from PV curve analysis: Relaxation, stiffness, equilibrium volume, elastic recoil","definition_or_measurement_approach":"Derived from pressure-volume (PV) curve analysis assessing relaxation, stiffness, equilibrium volume and elastic recoil."}

Secondary endpoints

• {"endpoint_text":"- Reverse geometric remodeling variables of the LV: Ventricular volumes and mass measured by cardiac magnetic resonance imaging (MRI)","definition_or_measurement_approach":"Left ventricular volumes and mass measured by cardiac MRI."}
• {"endpoint_text":"- Intraventricular flow patterns based on Doppler echocardiography and phase-contrast MRI: Vorticity parameters and blood transport into the LV; energy exchange between the myocardium and blood","definition_or_measurement_approach":"Intraventricular flow assessed by Doppler echocardiography and phase-contrast MRI, including vorticity parameters and measures of blood transport and energy exchange."}
• {"endpoint_text":"- Cardiomyocyte alterations: grade of hypertrophy assessed by morphometry and expression of pro-hypertrophic genes (atrial natriuretic peptide, sarcomeric proteins using real-time RT-PCR and western blot)","definition_or_measurement_approach":"Morphometry for hypertrophy grade; gene/protein expression assessed by real-time RT-PCR and western blot for specified markers."}
• {"endpoint_text":"- Interstitial and perivascular fibrosis","definition_or_measurement_approach":"Histological assessment of interstitial and perivascular fibrosis (presumed from biopsy assessments)."}
• {"endpoint_text":"- Degree of collagen crosslinking","definition_or_measurement_approach":"Biochemical/histological measures to quantify collagen crosslinking (as specified in protocol)."}
• {"endpoint_text":"- Microvascular alterations","definition_or_measurement_approach":"Assessment of microvascular abnormalities (methods as per protocol, e.g., histology/imaging)."}
• {"endpoint_text":"- Cardiomyocyte stiffness: Titin","definition_or_measurement_approach":"Measurement of titin-related cardiomyocyte stiffness (molecular/histological assays as per protocol)."}
• {"endpoint_text":"- Extracellular matrix: Lysyl-oxidases and hydroxylases, miR-19b, WISPER, and AGEs","definition_or_measurement_approach":"Molecular assays quantifying specified extracellular matrix components and markers (lysyl-oxidases, hydroxylases, miR-19b, WISPER, AGEs)."}
• {"endpoint_text":"- Cardiomyocytes: NT-proBNP, high-sensitivity troponin T (TnT)","definition_or_measurement_approach":"Circulating biomarkers measured in blood: NT-proBNP and high-sensitivity troponin T."}

Spain

Earliest CTIS Part Ii Submission Date

30-01-2025

Latest Decision Or Authorization Date

31-01-2025

Processing Time Days

1

Number Of Sites

1

Number Of Participants

20

Primary sponsor

Full Name

Fundación para la Innovación en Biomedicina

Organisation Type

SME

Country Of Registered Address

Spain

Co-sponsors

• Fundacion Para La Investigacion Biomedica Del Hospital Gregorio Maranon