Polydiuretic Therapy for HFpEF, a Randomised Controlled Trial

• Status: Not yet recruiting
• Trial end date: 2023-01-01
• Target enrollment: 0
• Participant gender: All

Summary

Heart Failure (HF) in Australia affects 1-2% of the population. Heart failure with preserved ejection fraction (HFpEF) refers to a syndrome of clinical heart failure without impairment of systolic cardiac function. HFpEF has few therapeutic agents that are proven to improve outcomes and it was only recently, the published EMPEROR-Preserved trial demonstrated that empagliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2i) reduced composite outcome of heart failure hospitalisation and cardiovascular death by 21% among patients with HFpEF.[1] HFpEF therapies have traditionally aimed at providing symptomatic relief and treating coexisting illnesses.

This multi-centre randomised clinical trial aims to establish the feasibility of a fixed low dose combination polypill consisting of bumetanide 0.5 mg, eplerenone 25 mg, and empagliflozin 10 mg in patients with HFpEF compared against empagliflozin 10 mg monotherapy in patients with HFpEF.

Fixed dose combination low dose diuretics of this nature have not been rigorously studied in patients with HFpEF, and this study aims to help improve the treatment paradigm for this patient population.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The George Institute
• Collaborators: St Vincent's Centre for Applied Medical Research; Victor Chang Cardiac Research Institute
• Treatments: Bumetanide; Empagliflozin; Eplerenone

Criteria

Inclusion Criteria:

1. Have provided written informed consent

2. Adults ≥ 18 years old

3. Established diagnosis of NYHA Class II - IV heart failure with preserved ejection fraction, which has been present for at least 2 months

4. 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.

5. 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)

Exclusion Criteria:

1. Known contraindication to bumetanide, eplerenone, or empagliflozin.

2. Concurrently prescribed prohibited medications which are mineralocorticoid receptor antagonists (Spironolactone and Eplerenone) and SGLT2i agents.

3. Symptomatic hypotension or systolic BP <95 mmHg at 2 out of 3 measurements at Visit 0

4. Current acute decompensated HF or hospitalisation due to decompensated HF <4 weeks prior to enrolment.

5. Myocardial infarction, unstable angina, stroke, or transient ischaemic attack (TIA) within 12 weeks prior to enrolment.

6. HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy or uncorrected primary valvular disease or reduced EF < 50%

7. Symptomatic bradycardia or second or third-degree heart block without a pacemaker.

8. 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).

9. Previous history of ketoacidosis

10. 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).

11. 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.

12. 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.

13. Participant's responsible primary care or other responsible physician believes it is not appropriate for participant to participate in the study.

14. Inability or unwillingness to provide written informed consent.

15. Involvement in the planning and/or conduct of the study.