Stable symptomatic heart failure with reduced ejection fraction (HFrEF) MedDRA version: 20.0 Level: HLGT Classification code 10019280 Term: Heart failures System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Pharmaceutical Form: Tablet
INN or Proposed INN: DAPAGLIFLOZIN PROPANEDIOL MONOHYDRATE
CAS Number: 960404-48-2
Other descriptive name: DAPAGLIFLOZIN PROPANEDIOL MONOHYDRATE
Concentration unit: mg mill
Sponsors
Instituto de Investigación Sanitaria INCLIVA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -The participant or his legal representative is willing and able to give informed consent for participation in the study. - Male or female, aged =18 years. - Established documented diagnosis of symptomatic HF (NYHA functional class II-III), which has been present for at least 2 months. - LVEF =40% documented in the last 3 months by echocardiography or cardiac magnetic resonance. - Established diagnosis of type 2 diabetes. - NT-proBNP =600 pg/ml. - Patients should receive background standard of care for HFrEF at judgment of the investigator. - Estimated glomerular filtration rate (eGFR) =30 ml/min/1.73m2 (DMRD formula) at enrolment. 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 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
Exclusion criteria: - Patients receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrolment, or previous intolerance of an SGLT2 inhibitor. - Type 1 diabetes. - Symptomatic hypotension or systolic blood pressure <95 mmHg. - Current acute decompensated HF or hospitalization due to decompensated HF <4 weeks prior to enrolment. - Myocardial infarction, unstable angina, stroke, or transient ischemic attack within 12 weeks prior to enrolment. - Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) or cardiac valve repair/replacement within 12 weeks prior to enrolment, or planned to undergo any of these operations after randomization. - Implantation of a cardiac resynchronization therapy (CRT) device within 12 weeks prior to enrolment or intent to implant a CRT device. - Previous cardiac transplantation or implantation of a ventricular assistance device or similar device, or implantation expected after randomization. - HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy, or uncorrected severe primary cardiac valve disease. - Symptomatic bradycardia or second or third-degree heart block without a pacemaker. - Severe renal dysfunction (eGFR<30 ml/min/1.73m2) or prior admission for acute renal failure in the last 4 weeks. - Pregnant or lactating women. - Woman of childbearing age, unless they are using highly effective contraceptive methods. - Patients with severe hepatic impairment (Child-Pugh class C).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To quantify changes in 6MWT, MLHFQ, surrogates of HF severity [amino-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), ST-2, and galectin-3], markers of congestion (clinical signs, plasma CA125, bioimpedance, and renal echo doppler), urine biomarkers (tubule markers, serum sodium, serum potassium, and glucose), and metabolomics (determination of ketones), at 30 and 90 days after the initiation of dapagliflozin vs. placebo.;Primary end point(s): Changes in peakVO2.;Timepoint(s) of evaluation of this end point: at 30 and 90 days after starting treatment with dapagliflozin vs. placebo.;Main Objective: To determine and quantify the changes in peakVO2 at 30 and 90 days after starting treatment with dapagliflozin vs. placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Changes in 6MWT, MLHFQ, surrogates of HF severity [amino-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), ST-2, and galectin-3], markers of congestion (clinical signs, plasma CA125, bioimpedance, and renal echo doppler), urine biomarkers (tubule markers, serum sodium, serum potassium, and glucose), and metabolomics (determination of ketones).;Timepoint(s) of evaluation of this end point: At 30 and 90 days after the initiation of dapagliflozin vs. placebo. | — |
Countries
Spain
Contacts
Public ContactScientific Subdirector
Instituto de Investigación Sanitaria INCLIVA
Outcome results
None listed