Heart Failure With Preserved Ejection Fraction Clinical Trial
Official title:
Polydiuretic Therapy for Heart Failure With Preserved Ejection Fraction: A Pilot Trial
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.
Status | Recruiting |
Enrollment | 30 |
Est. completion date | June 1, 2024 |
Est. primary completion date | December 31, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
Australia | Royal Prince Alfred Hospital | Camperdown | New South Wales |
Australia | St Vincent's Hospital Sydney | Darlinghurst | New South Wales |
Lead Sponsor | Collaborator |
---|---|
The George Institute | St Vincent's Centre for Applied Medical Research, Victor Chang Cardiac Research Institute |
Australia,
Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Bohm M, Brunner-La Rocca HP, Choi DJ, Chopra V, Chuquiure-Valenzuela E, Giannetti N, Gomez-Mesa JE, Janssens S, Januzzi JL, Gonzalez-Juanatey JR, Merkely B, Nicholls SJ, Perrone SV, Pina IL, Ponikowski P, Senni M, Sim D, Spinar J, Squire I, Taddei S, Tsutsui H, Verma S, Vinereanu D, Zhang J, Carson P, Lam CSP, Marx N, Zeller C, Sattar N, Jamal W, Schnaidt S, Schnee JM, Brueckmann M, Pocock SJ, Zannad F, Packer M; EMPEROR-Preserved Trial Investigators. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med. 2021 Oct 14;385(16):1451-1461. doi: 10.1056/NEJMoa2107038. Epub 2021 Aug 27. — View Citation
Bozkurt B, Coats AJ, Tsutsui H, Abdelhamid M, Adamopoulos S, Albert N, Anker SD, Atherton J, Bohm M, Butler J, Drazner MH, Felker GM, Filippatos G, Fonarow GC, Fiuzat M, Gomez-Mesa JE, Heidenreich P, Imamura T, Januzzi J, Jankowska EA, Khazanie P, Kinugawa K, Lam CSP, Matsue Y, Metra M, Ohtani T, Francesco Piepoli M, Ponikowski P, Rosano GMC, Sakata Y, SeferoviC P, Starling RC, Teerlink JR, Vardeny O, Yamamoto K, Yancy C, Zhang J, Zieroth S. Universal Definition and Classification of Heart Failure: A Report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure. J Card Fail. 2021 Mar 1:S1071-9164(21)00050-6. doi: 10.1016/j.cardfail.2021.01.022. Online ahead of print. — View Citation
Sahle BW, Owen AJ, Mutowo MP, Krum H, Reid CM. Prevalence of heart failure in Australia: a systematic review. BMC Cardiovasc Disord. 2016 Feb 6;16:32. doi: 10.1186/s12872-016-0208-4. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Exploratory Endpoint | Changes in health-related quality of life measured by the Kansas City Cardiomyopathy Questionnaire from baseline to 4 weeks (scaled results 0-100 and higher number is reflective of a better outcome) | 4 weeks | |
Other | Incidence of Serious adverse events and Adverse events of special interest (safety and tolerability) | Incidence of treatment-emergent serious and special interest adverse events (Safety and Tolerability) | 4 weeks | |
Primary | Feasibility of recruitment and compliance with study protocol (30 participants and 80% participant completion of study protocol) | Recruitment of 30 participants, with completion of study related procedures (screening, randomisation, study drug allocation, follow-up procedures, and retention over 4 weeks) in = 80% of participants. | 6 months | |
Secondary | NT-proBNP | Change in NT-proBNP (ng/L) from baseline to 4 weeks | 4 weeks | |
Secondary | NYHA Class | Change in NYHA Class (I-IV) from baseline to 4 weeks | 4 weeks | |
Secondary | 6-minute Walk Test (6MWT) distance | Change in 6MWT distance (metres) from baseline to 4 weeks | 4 weeks | |
Secondary | Systolic and Diastolic Blood Pressure | Change in systolic and diastolic blood pressure (mmHg) from baseline to 4 weeks | 4 weeks | |
Secondary | Body Weight | Change in body weight from baseline to 4 weeks (Kg) | 4 weeks | |
Secondary | Haemoglobin A1c | Change in haemoglobin A1c (mmol//mol and %) from baseline to 4 weeks | 4 weeks | |
Secondary | Haemoglobin and haematocrit | Change in haemoglobin (g/L) and haematocrit from baseline to 4 weeks | 4 weeks | |
Secondary | Renal Function | Change in renal function measured by creatinine(umol/L) and estimated glomerular filtration rate (ml/min/1.73m2) from baseline to 4 weeks | 4 weeks | |
Secondary | Potassium | Change in blood potassium concentration (mmol/L) from baseline to 4 weeks | 4 weeks | |
Secondary | Total Diuretic Dose | Change in total diuretic dose from baseline to 4 weeks | 4 weeks | |
Secondary | Pill Burden | Number of pills taken during 4-week trial period | 4 weeks |
Status | Clinical Trial | Phase | |
---|---|---|---|
Suspended |
NCT05839730 -
Fast Induced Remodeling in Heart Failure With Preserved Ejection Fraction
|
N/A | |
Recruiting |
NCT05095688 -
Relationship Between Adipose Tissue Distribution and Arterial Stiffness in HFpEF
|
||
Recruiting |
NCT06379152 -
Effect of Bilirubin on Prognosis in Heart Failure With Preserved Ejection Fraction
|
||
Recruiting |
NCT05676684 -
Dapagliflozin, Spironolactone or Both for HFpEF
|
Phase 2/Phase 3 | |
Recruiting |
NCT04153136 -
Effects of Sacubitril/Valsartan on Subclinical Heart Failure in HIV (The ENCHANTMENT HIV Study)
|
Phase 2 | |
Recruiting |
NCT06114498 -
Hospital Register of Decompensated Heart Failure With Preserved Ejection Fraction
|
||
Recruiting |
NCT05715697 -
Renal Denervation in Patients With Chronic Heart Failure With Preserved Ejection Fraction
|
N/A | |
Recruiting |
NCT04745013 -
PeRsonalIzed remOtely Guided Preventive exeRcIse Therapy for a healThY Heart
|
N/A | |
Completed |
NCT05126836 -
Cilostazol for HFpEF
|
Phase 2 | |
Completed |
NCT05586828 -
A Single-center Retrospective Cohort Study to Explore the Prognostic Significance of CONUT in Elderly CAD Patients With HFpEFand Compare CONUT With Other Objective Nutritional Indices.
|
||
Recruiting |
NCT04594499 -
The Relationship Between Pericardial Fat Thickness and Arterial Stiffness in HFpEF Patients
|
||
Active, not recruiting |
NCT05204238 -
Follow Up of acuTe Heart failUre: a pRospective Echocardiographic and Clinical Study (FUTURE)
|
||
Completed |
NCT04535726 -
The Relationship Between Blood Pressure and Arterial Stiffness in HFpEF Patients With Different Levels of Obesity
|
||
Recruiting |
NCT03550235 -
Exploration of Dyspnea at Non-high Brain Natriuretic Peptide (BNP)
|
||
Completed |
NCT04633460 -
Acute Effects of Exogenous Ketone Ester Administration in Heart Failure
|
Phase 2 | |
Completed |
NCT06228807 -
Clinical Characteristics and Predictors of Adverse Outcomes in HFpEF
|
||
Active, not recruiting |
NCT05284617 -
Exploratory Ph 2A, Double-Blind, Placebo-Controlled Dose Escalation Study of Safety, Tolerability, PD, & PK of HU6 for Subjects With Obese HFpEF
|
Phase 2 | |
Recruiting |
NCT05562063 -
Sotagliflozin in Heart Failure With Preserved Ejection Fraction (HFpEF) Patients
|
Phase 4 | |
Recruiting |
NCT06027307 -
Enavogliflozin Outcome Trial in Functional Tricuspid Regurgitation
|
Phase 3 | |
Withdrawn |
NCT05322616 -
Single-Ascending Dose Study of JK07 in Subjects With HFpEF
|
Phase 1 |