Heart Failure Patients with Reduced Ejection Fraction (HFrEF) MedDRA version: 20.0 Level: LLT Classification code 10078289 Term: Heart failure with reduced ejection fraction System Organ Class: 100000004849
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of signed informed consent prior to any study specific procedures 2. Male or female, aged =18 years 3. Documented diagnosis of symptomatic HF (NYHA functional class II-IV), which has been present for at least 8 weeks, optimally treated with pharmacotherapy and/or device therapy with at least intermittent need for diuretic treatment. 4. LVEF=40% within the last 12 months prior to enrolment. 5. NT-proBNP =400 pg/mL (or if hospitalised for heart failure within the previous 12 months: NT-proBNP =300 pg/mL) at enrolment. If concomitant atrial fibrillation NT-proBNP must be =800 pg/mL (irrespective of history of heart failure hospitalisation) 6. Patients should receive background standard of care as described below: All HFrEF patients should be treated according to locally recognised guidelines on standard of care treatment with both drugs and devices, as appropriate. Guideline-recommended medications should be used at recommended doses unless contraindicated or not tolerated. Therapy should have been individually optimised and stable for =4 weeks (this does not apply to diuretics) before visit 1 and include (unless contraindicated or not tolerated): • an ACE inhibitor, or ARB or sacubitril/valsartan and • a beta-blocker and • if considered appropriate by the patient's treating physician; a mineral corticoid receptor antagonist 7. 6MWD=100 metres and =425 metres at both the Enrolment and Randomisation. 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 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 150
Exclusion criteria
Exclusion criteria: 1. Presence of any condition that precludes exercise testing. 2. Participation in a structured exercise training programme in the 1 month prior to screening or planned to start during the trial. 3. Receiving therapy with an SGLT2 inhibitor within 4 weeks prior to randomisation or previous intolerance to an SGLT2 inhibitor. 4. Type 1 diabetes mellitus. 5. eGFR <25 mL/min/1.73 m2 (CKD-EPI formula) at visit 1, unstable or rapidly progressing renal disease at time of randomisation. 6. Systolic BP <95 mmHg on 2 consecutive measurements at 5-minute intervals, at Visit 1 or at Visit 2a/b. 7. Systolic BP =160 mmHg if not on treatment with =3 blood pressure lowering medications or =180 mmHg irrespective of treatments, on 2 consecutive measurements at 5-minute intervals, at Visit 1 (Enrolment) or at Visit 2a/b 8. Current acute decompensated HF or hospitalisation due to decompensated HF <4 weeks prior to enrolment. 9. Myocardial infarction, unstable angina, coronary revascularization ablation of atrial flutter/fibrillation, valve repair/replacement, implantation of a cardiac resynchronization therapy device within 12 weeks prior to enrolment. 10. Planned coronary revascularization, ablation of atrial flutter/fibrillation and/or valve repair/replacement. 11. Stroke or transient ischemic attack within 12 weeks prior to enrolment. 12. Probable alternative or concomitant diagnoses which could account for the patient's HF symptoms and signs. 13. Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD. 14. Previous cardiac transplantation, or complex congenital heart disease. Planned cardiac resynchronisation therapy. Prior implantation of a ventricular assistance device or similar device, or implantation expected after randomization. 15. HF due to any of the following: known infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac tamponade, known genetic hypertrophic cardiomyopathy or obstructive hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy/dysplasia, or uncorrected primary valvular disease. 16. A life expectancy of <2 years due to any non-cardiovascular condition, based on Investigator's clinical judgement. 17. Active malignancy requiring treatment (with the exception of basal cell or squamous cell carcinomas of the skin). 18. Acute or chronic liver disease with severe impairment of liver function (eg, ascites, oesophageal varices, coagulopathy). 19. Women of child-bearing potential not willing to use a medically accepted method of contraception considered reliable in the judgment of the Investigator OR who have a positive urine pregnancy test at randomisation OR who are breast-feeding. 20. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca personnel and/or personnel at the study site). 21. Previous randomisation in the present study. 22. Participation in another clinical study with an IP or device during the last month prior to enrolment. 23. Inability of the patient, in the opinion of the Investigator, to understand and/or comply with study23 Inability of the patient, in the opinion of the Investigator, to understand and/or comply with study medications, procedures and/or follow-up (especially completing ePRO assessments) OR any conditions that, in the opinion of the Investigator, may render the patient unable to complete the study. Therefore, patients who are unable to read (eg, are blind
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether dapagliflozin is superior to placebo in patients with chronic heart failure with the New York Heart Association (NYHA) Functional Class II-IV (range I-IV, higher class represents worse functional class) and reduced ejection fraction (LVEF=40%) [HFrEF] in: - reducing patient-reported HF symptoms - reducing patient-reported physical limitation - improving exercise capacity;Secondary Objective: To determine whether dapagliflozin is superior to placebo in increasing time spent non-sedentary, evaluated in a subset of at least 100 patients;Primary end point(s): - Change from baseline in Kansas-City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) at Week16 (higher scores represent less HF symptom frequency and burden). - Change from baseline in Kansas-City Cardiomyopathy Questionnaire-Physical Limitation Score (KCCQ-PLS) at Week16 (higher scores represent less physical limitation due to HF) - Change from baseline in 6-minute walk distance (6MWD) at Week16 (larger distances represent better functional capacity).;Timepoint(s) of evaluation of this end point: At baseline and at Week16 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change from baseline at the end of the study in the total time spent in light to vigorous physical activity, as assessed using a wearable activity monitor (accelerometer).;Timepoint(s) of evaluation of this end point: From baseline until the week starting at Week14. | — |
Countries
Brazil, Canada, Denmark, Japan, Korea, Democratic People's Republic of, Slovakia, South Africa, Sweden, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed