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

NCT05964738 | Completed Phase 2

• 1 other identifier: REDICAE
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Heart Failure; Electric Impedance; Dyspnea; Safety; Withdrawal

Keywords

Heart Failure; Diuretics; Dyspnea; Safety; Fluid overload; Withdraw; Electric Impedance

Outcome Measures

Primary Outcomes (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.

  baseline - 30 days - 90 days - 180 days

Secondary Outcomes (12)

• Acute decompensated heart failure events

  180 days

• Variation of plasmatic levels of natriuretic peptides

  baseline - 30 days - 90 days - 180 days

• Tissue fluid overload

  baseline - 30 days - 90 days - 180 days

• Body Composition Monitor (BCM) of Fresenius Medical Care

  baseline - 30 days - 90 days - 180 days

• Inferior vena cava (IVC) diameter

  baseline - 30 days - 90 days - 180 days

Study Arms (2)

Diuretics withdrawal

EXPERIMENTAL

Drug: Diuretics withdrawal

Diuretics maintenance

ACTIVE COMPARATOR

Drug: Diuretics maintenance

Interventions

Diuretics withdrawal DRUG

Diuretics that not have been demonstrated improve survival in chronic HFrEF are withdrawn

Diuretics withdrawal

Diuretics maintenance DRUG

Any diuretic could be used

Diuretics maintenance

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Maimónides Biomedical Research Institute of Córdoba: lead
• Sociedad Andaluza de Cardiología: collaborator

Study Sites (1)

Hospital Universitario Reina Sofía

Córdoba, Córdoba (Andalucía), 14004, Spain

Location

Related Publications (9)

• 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.

  PMID: 34447992 BACKGROUND

• 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.

  PMID: 25176015 BACKGROUND

• 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.

  PMID: 30741494 BACKGROUND

• 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.

  PMID: 32673497 BACKGROUND

• 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.

  PMID: 33736819 BACKGROUND

• 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.

  PMID: 31424503 BACKGROUND

• 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.

  PMID: 28390780 BACKGROUND

• 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.

  PMID: 32171764 BACKGROUND

• 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.

  PMID: 21791539 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Dyspnea; Edema

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Alberto Torres Zamudio, MD

  Hospital Universitario Reina Sofía de Córdoba

  PRINCIPAL INVESTIGATOR

• Juan Carlos Castillo Domínguez, MD, PhD

  Maimónides Biomedical Research Institute of Córdoba

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2023
• First Posted: July 28, 2023
• Study Start: December 19, 2022
• Primary Completion: October 31, 2024
• Study Completion: October 31, 2024
• Last Updated: November 4, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: From October 2024
• Access Criteria: Contact by email with Central Contact Person

Locations

ES (1)