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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT05129722
Registration number
NCT05129722
Ethics application status
Date submitted
7/11/2021
Date registered
22/11/2021
Date last updated
25/05/2023
Titles & IDs
Public title
Polydiuretic Therapy for HFpEF, a Randomised Controlled Trial
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Scientific title
Polydiuretic Therapy for Heart Failure With Preserved Ejection Fraction: A Pilot Trial
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Secondary ID [1]
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2021/PID02198
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Heart Failure With Preserved Ejection Fraction
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Condition category
Condition code
Cardiovascular
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Coronary heart disease
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Cardiovascular
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Other cardiovascular diseases
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Low dose combination polydiuretic therapy
Treatment: Drugs - Comparator monotherapy empagliflozin
Experimental: Patients receiving low dose combination polydiuretic therapy - This patient group will receive a low dose combination polydiuretic therapy treatment consisting of: bumetanide 0.5 mg (loop diuretic), eplerenone 25 mg (mineralocorticoid receptor antagonist) and empagliflozin 10mg (sodium-glucose co-transporter 2 inhibitor) daily on top of their background therapy.
Active Comparator: Comparator group receiving monotherapy empagliflozin - This comparator patient group will receive empagliflozin 10mg (sodium-glucose co-transporter 2 inhibitor) daily on top of their background therapy.
Treatment: Drugs: Low dose combination polydiuretic therapy
Low dose combination polydiuretic therapy treatment consists of:
Loop diuretic bumetanide 0.5 mg Mineralocorticoid receptor antagonist eplerenone 25 mg Sodium-glucose co-transporter 2 inhibitor (SGLT2i): empagliflozin 10mg
Treatment: Drugs: Comparator monotherapy empagliflozin
Sodium-glucose co-transporter 2 inhibitor (SGLT2i): empagliflozin 10mg
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Feasibility of recruitment and compliance with study protocol (30 participants and 80% participant completion of study protocol)
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Assessment method [1]
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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.
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Timepoint [1]
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6 months
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Secondary outcome [1]
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NT-proBNP
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Assessment method [1]
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Change in NT-proBNP (ng/L) from baseline to 4 weeks
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Timepoint [1]
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4 weeks
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Secondary outcome [2]
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NYHA Class
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Assessment method [2]
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Change in NYHA Class (I-IV) from baseline to 4 weeks
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Timepoint [2]
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4 weeks
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Secondary outcome [3]
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6-minute Walk Test (6MWT) distance
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Assessment method [3]
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Change in 6MWT distance (metres) from baseline to 4 weeks
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Timepoint [3]
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4 weeks
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Secondary outcome [4]
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Systolic and Diastolic Blood Pressure
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Assessment method [4]
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Change in systolic and diastolic blood pressure (mmHg) from baseline to 4 weeks
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Timepoint [4]
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4 weeks
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Secondary outcome [5]
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Body Weight
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Assessment method [5]
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Change in body weight from baseline to 4 weeks (Kg)
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Timepoint [5]
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4 weeks
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Secondary outcome [6]
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Haemoglobin A1c
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Assessment method [6]
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Change in haemoglobin A1c (mmol//mol and %) from baseline to 4 weeks
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Timepoint [6]
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4 weeks
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Secondary outcome [7]
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Haemoglobin and haematocrit
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Assessment method [7]
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Change in haemoglobin (g/L) and haematocrit from baseline to 4 weeks
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Timepoint [7]
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4 weeks
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Secondary outcome [8]
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Renal Function
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Assessment method [8]
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Change in renal function measured by creatinine(umol/L) and estimated glomerular filtration rate (ml/min/1.73m2) from baseline to 4 weeks
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Timepoint [8]
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4 weeks
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Secondary outcome [9]
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Potassium
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Assessment method [9]
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Change in blood potassium concentration (mmol/L) from baseline to 4 weeks
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Timepoint [9]
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4 weeks
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Secondary outcome [10]
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Total Diuretic Dose
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Assessment method [10]
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Change in total diuretic dose from baseline to 4 weeks
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Timepoint [10]
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4 weeks
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Secondary outcome [11]
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Pill Burden
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Assessment method [11]
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Number of pills taken during 4-week trial period
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Timepoint [11]
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4 weeks
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Eligibility
Key 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)
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 4
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/10/2022
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
1/06/2024
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Actual
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Sample size
Target
30
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
NSW
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Recruitment hospital [1]
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Royal Prince Alfred Hospital - Camperdown
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Recruitment hospital [2]
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St Vincent's Hospital Sydney - Darlinghurst
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Recruitment postcode(s) [1]
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2050 - Camperdown
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Recruitment postcode(s) [2]
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2010 - Darlinghurst
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Funding & Sponsors
Primary sponsor type
Other
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Name
The George Institute
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Address
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Country
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Other collaborator category [1]
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Other
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Name [1]
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Victor Chang Cardiac Research Institute
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Address [1]
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Country [1]
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Other collaborator category [2]
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Other
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Name [2]
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St Vincent's Centre for Applied Medical Research
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Address [2]
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Country [2]
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Ethics approval
Ethics application status
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Summary
Brief 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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT05129722
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Trial related presentations / publications
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.
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.
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.
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Public notes
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Contacts
Principal investigator
Name
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Clare Arnott
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Address
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The George Institute
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Clare Arnott
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Address
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Country
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Phone
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+61 2 8052 4823
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT05129722
Download to PDF