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Heart FailurePhase 2REDICAENCT05964738

Effect of Diuretics Withdrawal in Chronic Heart Failure With Reduced Ejection Fraction

A Phase 2 study testing Diuretics withdrawal and Diuretics maintenance in people with Heart Failure and Electric Impedance, run by Maimónides Biomedical Research Institute of Córdoba at 1 site in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

REDICAE trial was designed to evaluate the safety and tolerability of diuretics withdrawal in stable, euvolemic chronic outpatients with heart failure with reduced ejection fraction. It is a single-center, randomized, open-label, phase II clinical trial. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Heart Failure, Electric Impedance, Dyspnea
What is being tested?
Diuretics withdrawal and Diuretics maintenance
Could I receive a placebo?
No, everyone receives an active treatment
How many people
98 participants
Where
1 siteSpain
Study dates
19 Dec 2022to 31 Oct 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Outpatients diagnosed of chronic HFrEF by criteria of ESC Guidelines of 2021
  • Age equal or greater than 18 year-old
  • Stable and euvolemic outpatients determined by clinical criteria, biomarkers (CA-125 < 23 U/mL) and bioelectrical impedance analysis
  • Left Ventricular Ejection Fraction less than 50% by echocardiography or cardiovascular magnetic resonance performed within 6 months before the screening visit
  • New York Heart Association functional class I or II
  • No episodes of acute decompensated heart failure within 2 months before the screening visit
Show all 9Show fewer
  • Treatment with a stable dose of diuretic for at least 1 month before the screening visit
  • Optimal medical therapy with ACEI/ARNI, BB, MRA and iSGLT2 must be started to titration unless any of them were contraindicated or not tolerated
  • Plasma potassium < 5 mg/dl in the screening visit

Who cannot join

  • Acute coronary syndrome within 3 months before screening visit
  • Awaiting cardiac resynchronization therapy
  • Any severe valve heart disease not yet treated
  • Pulmonary hypertension or any severe pulmonary disease
  • End-stage chronic kidney disease (on hemodialysis). Acute kidney injury
  • Severe hepatic failure or cirrhosis
Show all 11Show fewer
  • Malignancy on active treatment
  • Congenital heart disease
  • Awaiting cardiac transplantation
  • Inability to understand and sign the informed consent
  • Participation in any other interventional clinical research

Trial locations and contacts

1 site in 1 country.

Spain1 site

  • Hospital Universitario Reina Sofía

    Córdoba, Córdoba (Andalucía), 14004

Other trials in Spain

About this study

Official title: Safety and Tolerability of Diuretics Withdrawal in Heart Failure With Reduced Ejection Fraction. REDICAE Trial.

REDICAE trial was designed to evaluate the safety and tolerability of diuretics withdrawal in stable, euvolemic chronic outpatients with heart failure with reduced ejection fraction. It is a single-center, randomized, open-label, phase II clinical trial.

Read the detailed description

Treatment of heart failure with reduced ejection fraction (HFrEF) has improved patient survival in recent decades. Diuretics are essentials in acute decompensated heart failure, specially furosemide. However, when patients are stable and euvolemic diuretics (loop diuretics, thiazide diuretics or acetazolamide) might increase adverse effects: renin-angiotensin-aldosterone system activation, renal function impairment or electrolyte disturbances.

The 2021 European Society of Cardiology (ESC) Guidelines for the diagnosis and treatment of acute and chronic heart failure recommend angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor-neprilysin inhibitor (ARNI), beta-blockers (BB), mineralocorticoid receptor antagonists (MRA) and sodium-glucose co-transporter 2 inhibitors (iSTLT2) as first-line therapy for HFrEF. A significant proportion of patients take a maintenance diuretics dose despite the clinical benefits and prognosis are controversial.

Current clinical guidelines suggest that diuretic use can be reduced or discontinued in selected euvolemic or hypovolemic patients. This statement is based on the results of the ReBIC-1 trial published in 2019, which showed a neutral effect of furosemide discontinuation in stable chronic outpatients with HFrEF treated according to the 2016 ESC heart failure guidelines standards of care.

REDICAE trial was designed to evaluate the safety and tolerability of diuretics withdrawal, not just furosemide, in stable euvolemic chronic outpatients with HFrEF. It is a single-center, randomized, open-label phase II clinical trial.

The pathophysiology of congestion in heart failure is complex and multifactorial. In the REDICAE trial, volume status will be determined by biomarkers, echocardiography and bioelectrical impedance analysis. The patients enrolled in the study will be under contemporary guideline-directed medical therapy, including SGLT2 inhibitors. This trial is the largest prospective trial evaluating the clinical effects of diuretic discontinuation in HFrEF patients under contemporary pharmacological therapy for heart failure.

REDICAE trial develops in Hospital Universitario Reina Sofía in Cordoba (Spain)

Being tested
Diuretics withdrawal, Diuretics maintenance
Keywords
Heart Failure, Diuretics, Dyspnea, Safety, Fluid overload, Withdraw, Electric Impedance
Medical subject headings
Heart Failure, Dyspnea, Edema

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Diuretics withdrawalDrug

    Diuretics that not have been demonstrated improve survival in chronic HFrEF are withdrawn

  • Diuretics maintenanceDrug

    Any diuretic could be used

Study groups in NCT05964738
Study groupRoleWhat they receive
Diuretics withdrawalExperimentalNot described
Receives: Drug: Diuretics withdrawal
Diuretics maintenanceActive comparatorNot described
Receives: Drug: Diuretics maintenance

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in Dyspnea assessed by a visual analogue scale (VAS)

    VAS scores are scaled from 0 to 100 millimeters (mm). Higher scores mean a worse outcome.

    Measured: baseline - 30 days - 90 days - 180 days

Secondary outcomes (12)

  1. Acute decompensated heart failure events

    Number of Hospital admissions, emergency department visits or unscheduled medical appointments requiring intravenous diuretic treatment, and increase in diuretic dose or reintroduction of an oral diuretic.

    Measured: 180 days

  2. Variation of plasmatic levels of natriuretic peptides

    Levels of the N-terminal pro b-type natriuretic peptide (NT-proBNP)

    Measured: baseline - 30 days - 90 days - 180 days

  3. Tissue fluid overload

    Variation of plasmatic levels of antigen carbohydrate 125 (CA-125)

    Measured: baseline - 30 days - 90 days - 180 days

  4. Body Composition Monitor (BCM) of Fresenius Medical Care

    Variation of fluid overload assessed by bioelectrical impedance analysis

    Measured: baseline - 30 days - 90 days - 180 days

  5. Inferior vena cava (IVC) diameter

    IVC diameter measured in its intra-hepatic portion at 2 cm of the junction with the hepatic veins using a longitudinal view from a sub-xiphoid position. IVC is dilated when its diameter is more than 20 mm.

    Measured: baseline - 30 days - 90 days - 180 days

  6. Hepatic vein Doppler

    Pulsed wave Doppler shows a systolic (S) and diastolic (D) components. Normal pattern (S > D), mildly abnormal pattern (S < D) and severely abnormal pattern (S reverses)

    Measured: baseline - 30 days - 90 days - 180 days

  7. Portal vein Doppler

    Pulsed wave Doppler shows a continuous nonpulsatile flow. Using the pulsatility fraction (PF=100*[(Vmax - Vmin)/Vmax)]) are three patterns: normal PF < 30%, mildly abnormal PF 30-50% and severely abnormal PF >50%.

    Measured: baseline - 30 days - 90 days - 180 days

  8. Intra-renal venous Doppler

    Pulsed wave Doppler shows a normal pattern when flow is continuous. Mildly abnormal pattern shows a biphasic flow (S and D). Severely abnormal pattern shows a monophasic flow (D)

    Measured: baseline - 30 days - 90 days - 180 days

  9. Ultrasound congestion parameters by Venous Excess Ultrasound (VExUS) protocol

    IVC diameter, hepatic vein Doppler, portal vein Doppler and intra-renal venous Doppler patterns are combined to report VExUS grades:

    • Grade 0 (no congestion): IVC < 20 mm
    • Grade 1 (mild congestion): IVC ≥ 20 mm and any combination of normal or mildly abnormal pattern
    • Grade 2 (moderate congestion): IVC ≥ 20 mm + ≥ 1 severely abnormal pattern
    • Grado 4 (severe congestion): IVC ≥ 20 mm + ≥ 2 severely abnormal pattern

    Measured: baseline - 30 days - 90 days - 180 days

  10. Congestion assessed by lung ultrasound

    Pleural effusion or pathological B lines. More than two B lines are considered as pathological.

    Measured: baseline - 30 days - 90 days - 180 days

  11. Quality of life status

    Change From Baseline in the Kansas City Cardiomyopathy Questionnaire 12 (KCCQ-12) score. KCCQ-12 scores are scaled from 0 to 100. Higher scores mean a better outcome.

    Measured: baseline - 30 days - 90 days - 180 days

  12. 6 minute walk test

    Change From Baseline in meters walked, as assessed by the 6 minute walk test

    Measured: baseline - 30 days - 90 days - 180 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jul 2023
  2. Study start19 Dec 2022
  3. Primary completion31 Oct 2024
  4. Study completion31 Oct 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
98 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05964738
Sponsor's protocol ID
REDICAE
Acronym
REDICAE
Status last verified
Oct 2024
First submitted
28 Jun 2023
Last updated
4 Nov 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Contact by email with Central Contact Person

Publications

  • McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, Burri H, Butler J, Celutkiene J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021 Sep 21;42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. No abstract available.

    PubMed 34447992

  • McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. doi: 10.1056/NEJMoa1409077. Epub 2014 Aug 30.

    PubMed 25176015

  • Vardeny O, Claggett B, Kachadourian J, Desai AS, Packer M, Rouleau J, Zile MR, Swedberg K, Lefkowitz M, Shi V, McMurray JJV, Solomon SD. Reduced loop diuretic use in patients taking sacubitril/valsartan compared with enalapril: the PARADIGM-HF trial. Eur J Heart Fail. 2019 Mar;21(3):337-341. doi: 10.1002/ejhf.1402. Epub 2019 Feb 11.

    PubMed 30741494

  • Jackson AM, Dewan P, Anand IS, Belohlavek J, Bengtsson O, de Boer RA, Bohm M, Boulton DW, Chopra VK, DeMets DL, Docherty KF, Dukat A, Greasley PJ, Howlett JG, Inzucchi SE, Katova T, Kober L, Kosiborod MN, Langkilde AM, Lindholm D, Ljungman CEA, Martinez FA, O'Meara E, Sabatine MS, Sjostrand M, Solomon SD, Tereshchenko S, Verma S, Jhund PS, McMurray JJV. Dapagliflozin and Diuretic Use in Patients With Heart Failure and Reduced Ejection Fraction in DAPA-HF. Circulation. 2020 Sep 15;142(11):1040-1054. doi: 10.1161/CIRCULATIONAHA.120.047077. Epub 2020 Jul 16.

    PubMed 32673497

  • Packer M, Anker SD, Butler J, Filippatos G, Ferreira JP, Pocock SJ, Sattar N, Brueckmann M, Jamal W, Cotton D, Iwata T, Zannad F; EMPEROR-Reduced Trial Committees and Investigators. Empagliflozin in Patients With Heart Failure, Reduced Ejection Fraction, and Volume Overload: EMPEROR-Reduced Trial. J Am Coll Cardiol. 2021 Mar 23;77(11):1381-1392. doi: 10.1016/j.jacc.2021.01.033.

    PubMed 33736819

  • Rohde LE, Rover MM, Figueiredo Neto JA, Danzmann LC, Bertoldi EG, Simoes MV, Silvestre OM, Ribeiro ALP, Moura LZ, Beck-da-Silva L, Prado D, Sant'Anna RT, Bridi LH, Zimerman A, Raupp da Rosa P, Biolo A. Short-term diuretic withdrawal in stable outpatients with mild heart failure and no fluid retention receiving optimal therapy: a double-blind, multicentre, randomized trial. Eur Heart J. 2019 Nov 21;40(44):3605-3612. doi: 10.1093/eurheartj/ehz554.

    PubMed 31424503

  • Romano G, Vitale G, Bellavia D, Agnese V, Clemenza F. Is diuretic withdrawal safe in patients with heart failure and reduced ejection fraction? A retrospective analysis of our outpatient cohort. Eur J Intern Med. 2017 Jul;42:e11-e13. doi: 10.1016/j.ejim.2017.03.025. Epub 2017 Apr 6. No abstract available.

    PubMed 28390780

  • Nunez J, Bayes-Genis A, Revuelta-Lopez E, Ter Maaten JM, Minana G, Barallat J, Cserkoova A, Bodi V, Fernandez-Cisnal A, Nunez E, Sanchis J, Lang C, Ng LL, Metra M, Voors AA. Clinical Role of CA125 in Worsening Heart Failure: A BIOSTAT-CHF Study Subanalysis. JACC Heart Fail. 2020 May;8(5):386-397. doi: 10.1016/j.jchf.2019.12.005. Epub 2020 Mar 11.

    PubMed 32171764

  • Ekman I, Granger B, Swedberg K, Stenlund H, Boman K. Measuring shortness of breath in heart failure (SOB-HF): development and validation of a new dyspnoea assessment tool. Eur J Heart Fail. 2011 Aug;13(8):838-45. doi: 10.1093/eurjhf/hfr062.

    PubMed 21791539

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Diuretics withdrawal and Diuretics maintenance in people with Heart Failure and Electric Impedance, run by Maimónides Biomedical Research Institute of Córdoba at 1 site in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Dyspnea assessed by a visual analogue scale (VAS) (time frame: baseline - 30 days - 90 days - 180 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05964738, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2024.

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