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

October 31, 2024 updated by: Maimónides Biomedical Research Institute of Córdoba

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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)

Study Type

Interventional

Enrollment (Actual)

98

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
    • Córdoba (Andalucía)
      • Córdoba, Córdoba (Andalucía), Spain, 14004
        • Hospital Universitario Reina Sofia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Diuretics withdrawal
Drug: Diuretics withdrawal
Diuretics that not have been demonstrated improve survival in chronic HFrEF are withdrawn
Active Comparator: Diuretics maintenance
Drug: Diuretics maintenance
Any diuretic could be used

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Dyspnea assessed by a visual analogue scale (VAS)
Time Frame: baseline - 30 days - 90 days - 180 days
VAS scores are scaled from 0 to 100 millimeters (mm). Higher scores mean a worse outcome.
baseline - 30 days - 90 days - 180 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute decompensated heart failure events
Time Frame: 180 days
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.
180 days
Variation of plasmatic levels of natriuretic peptides
Time Frame: baseline - 30 days - 90 days - 180 days
Levels of the N-terminal pro b-type natriuretic peptide (NT-proBNP)
baseline - 30 days - 90 days - 180 days
Tissue fluid overload
Time Frame: baseline - 30 days - 90 days - 180 days
Variation of plasmatic levels of antigen carbohydrate 125 (CA-125)
baseline - 30 days - 90 days - 180 days
Body Composition Monitor (BCM) of Fresenius Medical Care
Time Frame: baseline - 30 days - 90 days - 180 days
Variation of fluid overload assessed by bioelectrical impedance analysis
baseline - 30 days - 90 days - 180 days
Inferior vena cava (IVC) diameter
Time Frame: baseline - 30 days - 90 days - 180 days
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.
baseline - 30 days - 90 days - 180 days
Hepatic vein Doppler
Time Frame: baseline - 30 days - 90 days - 180 days
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)
baseline - 30 days - 90 days - 180 days
Portal vein Doppler
Time Frame: baseline - 30 days - 90 days - 180 days
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%.
baseline - 30 days - 90 days - 180 days
Intra-renal venous Doppler
Time Frame: baseline - 30 days - 90 days - 180 days
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)
baseline - 30 days - 90 days - 180 days
Ultrasound congestion parameters by Venous Excess Ultrasound (VExUS) protocol
Time Frame: baseline - 30 days - 90 days - 180 days

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
baseline - 30 days - 90 days - 180 days
Congestion assessed by lung ultrasound
Time Frame: baseline - 30 days - 90 days - 180 days
Pleural effusion or pathological B lines. More than two B lines are considered as pathological.
baseline - 30 days - 90 days - 180 days
Quality of life status
Time Frame: baseline - 30 days - 90 days - 180 days
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.
baseline - 30 days - 90 days - 180 days
6 minute walk test
Time Frame: baseline - 30 days - 90 days - 180 days
Change From Baseline in meters walked, as assessed by the 6 minute walk test
baseline - 30 days - 90 days - 180 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Maimónides Biomedical Research Institute of Córdoba

Collaborators

Sociedad Andaluza de Cardiología

Investigators

  • Principal Investigator: Alberto Torres Zamudio, MD, Hospital Universitario Reina Sofía de Córdoba
  • Study Director: Juan Carlos Castillo Domínguez, MD, PhD, Maimónides Biomedical Research Institute of Córdoba

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 19, 2022

Primary Completion (Actual)

October 31, 2024

Study Completion (Actual)

October 31, 2024

Study Registration Dates

First Submitted

June 28, 2023

First Submitted That Met QC Criteria

July 25, 2023

First Posted (Actual)

July 28, 2023

Study Record Updates

Last Update Posted (Estimated)

November 4, 2024

Last Update Submitted That Met QC Criteria

October 31, 2024

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • REDICAE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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