search
Back to results

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

Primary Purpose

Heart Failure, Electric Impedance, Dyspnea

Status
Recruiting
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
Diuretics withdrawal
Diuretics maintenance
Sponsored by
Maimónides Biomedical Research Institute of Córdoba
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure focused on measuring Heart Failure, Diuretics, Dyspnea, Safety, Fluid overload, Withdraw, Electric Impedance

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA: 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 EXCLUSION CRITERIA: 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

Sites / Locations

  • Hospital Universitario Reina SofíaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Diuretics withdrawal

Diuretics maintenance

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Variation of plasmatic levels of natriuretic peptides
Levels of the N-terminal pro b-type natriuretic peptide (NT-proBNP)
Tissue fluid overload
Variation of plasmatic levels of antigen carbohydrate 125 (CA-125)
Body Composition Monitor (BCM) of Fresenius Medical Care
Variation of fluid overload assessed by bioelectrical impedance analysis
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.
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)
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%.
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)
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
Congestion assessed by lung ultrasound
Pleural effusion or pathological B lines. More than two B lines are considered as pathological.
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.
6 minute walk test
Change From Baseline in meters walked, as assessed by the 6 minute walk test

Full Information

First Posted
June 28, 2023
Last Updated
July 25, 2023
Sponsor
Maimónides Biomedical Research Institute of Córdoba
Collaborators
Sociedad Andaluza de Cardiología
search

1. Study Identification

Unique Protocol Identification Number
NCT05964738
Brief Title
Effect of Diuretics Withdrawal in Chronic Heart Failure With Reduced Ejection Fraction
Acronym
REDICAE
Official Title
Safety and Tolerability of Diuretics Withdrawal in Heart Failure With Reduced Ejection Fraction. REDICAE Trial.
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 19, 2022 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Maimónides Biomedical Research Institute of Córdoba
Collaborators
Sociedad Andaluza de Cardiología

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Electric Impedance, Dyspnea, Safety, Withdrawal
Keywords
Heart Failure, Diuretics, Dyspnea, Safety, Fluid overload, Withdraw, Electric Impedance

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Diuretics withdrawal
Arm Type
Experimental
Arm Title
Diuretics maintenance
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Diuretics withdrawal
Intervention Description
Diuretics that not have been demonstrated improve survival in chronic HFrEF are withdrawn
Intervention Type
Drug
Intervention Name(s)
Diuretics maintenance
Intervention Description
Any diuretic could be used
Primary Outcome Measure Information:
Title
Change From Baseline in Dyspnea assessed by a visual analogue scale (VAS)
Description
VAS scores are scaled from 0 to 100 millimeters (mm). Higher scores mean a worse outcome.
Time Frame
baseline - 30 days - 90 days - 180 days
Secondary Outcome Measure Information:
Title
Acute decompensated heart failure events
Description
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.
Time Frame
180 days
Title
Variation of plasmatic levels of natriuretic peptides
Description
Levels of the N-terminal pro b-type natriuretic peptide (NT-proBNP)
Time Frame
baseline - 30 days - 90 days - 180 days
Title
Tissue fluid overload
Description
Variation of plasmatic levels of antigen carbohydrate 125 (CA-125)
Time Frame
baseline - 30 days - 90 days - 180 days
Title
Body Composition Monitor (BCM) of Fresenius Medical Care
Description
Variation of fluid overload assessed by bioelectrical impedance analysis
Time Frame
baseline - 30 days - 90 days - 180 days
Title
Inferior vena cava (IVC) diameter
Description
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.
Time Frame
baseline - 30 days - 90 days - 180 days
Title
Hepatic vein Doppler
Description
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)
Time Frame
baseline - 30 days - 90 days - 180 days
Title
Portal vein Doppler
Description
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%.
Time Frame
baseline - 30 days - 90 days - 180 days
Title
Intra-renal venous Doppler
Description
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)
Time Frame
baseline - 30 days - 90 days - 180 days
Title
Ultrasound congestion parameters by Venous Excess Ultrasound (VExUS) protocol
Description
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
Time Frame
baseline - 30 days - 90 days - 180 days
Title
Congestion assessed by lung ultrasound
Description
Pleural effusion or pathological B lines. More than two B lines are considered as pathological.
Time Frame
baseline - 30 days - 90 days - 180 days
Title
Quality of life status
Description
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.
Time Frame
baseline - 30 days - 90 days - 180 days
Title
6 minute walk test
Description
Change From Baseline in meters walked, as assessed by the 6 minute walk test
Time Frame
baseline - 30 days - 90 days - 180 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: 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 EXCLUSION CRITERIA: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alberto Torres, MD
Phone
+34620650405
Email
atorzam.29@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alberto Torres Zamudio, MD
Organizational Affiliation
Hospital Universitario Reina Sofía de Córdoba
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Juan Carlos Castillo Domínguez, MD, PhD
Organizational Affiliation
Maimónides Biomedical Research Institute of Córdoba
Official's Role
Study Director
Facility Information:
Facility Name
Hospital Universitario Reina Sofía
City
Córdoba
State/Province
Córdoba (Andalucía)
ZIP/Postal Code
14004
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alberto Torres Zamudio, MD
Email
atorzam.29@gmail.com
First Name & Middle Initial & Last Name & Degree
Juan Carlos Castillo Domínguez, MD, PhD
First Name & Middle Initial & Last Name & Degree
Rafael González Manzanares, MD, PhD
First Name & Middle Initial & Last Name & Degree
José López Aguilera, MD, PhD
First Name & Middle Initial & Last Name & Degree
Manuel Anguita Sánchez, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Contact by email with Central Contact Person
IPD Sharing Time Frame
From October 2024
IPD Sharing Access Criteria
Contact by email with Central Contact Person
Citations:
PubMed Identifier
34447992
Citation
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. Erratum In: Eur Heart J. 2021 Oct 14;:
Results Reference
result
PubMed Identifier
25176015
Citation
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.
Results Reference
result
PubMed Identifier
30741494
Citation
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.
Results Reference
result
PubMed Identifier
32673497
Citation
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. Erratum In: Circulation. 2020 Nov 17;142(20):e369.
Results Reference
result
PubMed Identifier
33736819
Citation
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.
Results Reference
result
PubMed Identifier
31424503
Citation
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.
Results Reference
result
PubMed Identifier
28390780
Citation
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.
Results Reference
result
PubMed Identifier
32171764
Citation
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.
Results Reference
result
PubMed Identifier
21791539
Citation
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.
Results Reference
result

Learn more about this trial

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

We'll reach out to this number within 24 hrs