Polydiuretic Therapy for HFpEF, a Randomised Controlled Trial

Who can take part

• Have provided written informed consent
• Adults ≥ 18 years old
• Established diagnosis of NYHA Class II - IV heart failure with preserved ejection fraction, which has been present for at least 2 months
• Left ventricular ejection fraction ≥50% on echocardiography within the last 12 months prior to study enrolment, and no previous echocardiogram with EF < 40% NB: Patients in which additional pharmacological or device therapy is contemplated, or should be considered, must not be enrolled until therapy has been optimised and is stable for ≥ 1 month
• NT-proBNP >300 pg/ml (or if hospitalised for heart failure within the previous 12 months, NT-proBNP ≥400 pg/ml) at enrolment. If concomitant atrial fibrillation at Visit 1, NT-proBNP must be ≥900 pg/ml (irrespective of history of heart failure hospitalisation)

Who cannot take part

• Concurrently prescribed prohibited medications which are mineralocorticoid receptor antagonists (Spironolactone and Eplerenone) and SGLT2i agents
• Current acute decompensated HF or hospitalisation due to decompensated HF <4 weeks prior to enrolment
• Myocardial infarction, unstable angina, stroke, or transient ischaemic attack (TIA) within 12 weeks prior to enrolment
• Previous history of ketoacidosis
• Concomitant illness, physical impairment or mental condition which in the opinion of the study team / primary care physician could interfere with the conduct of the study including outcome assessment
• Participation in a concurrent interventional medical investigation or pharmacologic clinical trial. Participants in observational, natural history or epidemiological studies not involving an intervention are eligible
• HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease or reduced EF < 50%
• Symptomatic bradycardia or second or third-degree heart block without a pacemaker
• Evidence of secondary cause of hypertension e.g., renal artery stenosis; significant renal impairment (eGFR <50 ml/min/1.73 m2), raised serum potassium (above lab normal limit of 5.0 mEq/L)
• Known contraindication to bumetanide, eplerenone, or empagliflozin
• Symptomatic hypotension or systolic BP <95 mmHg at 2 out of 3 measurements at Visit 0
• Women who are pregnant, breast feeding or of childbearing potential and are not using and do not plan to continue using medically acceptable form of contraception throughout the study (pharmacological or barrier methods)
• Participant's responsible primary care or other responsible physician believes it is not appropriate for participant to participate in the study
• Inability or unwillingness to provide written informed consent
• Involvement in the planning and/or conduct of the study