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Completed

NCT Number: NCT05964738

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

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.

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Key information

Conditions

Heart Failure Cardiovascular Diseases Dyspnea Edema Electric Impedance Heart Diseases Pathological Conditions, Signs and Symptoms Respiration Disorders Respiratory Tract Diseases Safety Signs and Symptoms Signs and Symptoms, Respiratory Withdrawal

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Hospital Universitario Reina Sofía

Córdoba, Córdoba (Andalucía), 14004, Spain

About this study

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)

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Diuretics withdrawal

Drug

Diuretics that not have been demonstrated improve survival in chronic HFrEF are withdrawn

Diuretics maintenance

Drug

Any diuretic could be used

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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)

  3. Tissue fluid overload

    Time frame: baseline - 30 days - 90 days - 180 days

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

  4. 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

  5. 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.

  6. 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)

  7. 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%.

  8. 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)

  9. 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

  10. 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.

  11. 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.

  12. 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

Sponsors and collaborators

Lead sponsor

Maimónides Biomedical Research Institute of Córdoba

Other

Collaborators

  • Sociedad Andaluza de Cardiología

Registry information

Official study title

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

Acronym: REDICAE

Important dates

Study start
2022
Primary completion
2024
Study completion
2024
First posted
Jul 28, 2023
Registry last updated
Nov 4, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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