Clinical trial NCT05964738: Effect of Diuretics Withdrawal in Chronic Heart Failure with Reduced Ejection Fraction
Official title: Safety and Tolerability of Diuretics Withdrawal in Heart Failure with Reduced Ejection Fraction. REDICAE Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure
Electric Impedance
Dyspnea
Safety
Withdrawal
Keywords: Heart Failure
Diuretics
Dyspnea
Safety
Fluid overload
Withdraw
Electric Impedance
Lead sponsor: Maimónides Biomedical Research Institute of Córdoba
Sponsor class: OTHER
Collaborators: name: Sociedad Andaluza de Cardiología
First posted: 2023-07-28
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

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

Primary outcomes:
measure: Change From Baseline in Dyspnea assessed by a visual analogue scale (VAS)
timeFrame: baseline - 30 days - 90 days - 180 days
Secondary outcomes:
measure: Acute decompensated heart failure events
timeFrame: 180 days
measure: Variation of plasmatic levels of natriuretic peptides
timeFrame: baseline - 30 days - 90 days - 180 days
measure: Tissue fluid overload
timeFrame: baseline - 30 days - 90 days - 180 days
measure: Body Composition Monitor (BCM) of Fresenius Medical Care
timeFrame: baseline - 30 days - 90 days - 180 days
measure: Inferior vena cava (IVC) diameter
timeFrame: baseline - 30 days - 90 days - 180 days
measure: Hepatic vein Doppler
timeFrame: baseline - 30 days - 90 days - 180 days
measure: Portal vein Doppler
timeFrame: baseline - 30 days - 90 days - 180 days
measure: Intra-renal venous Doppler
timeFrame: baseline - 30 days - 90 days - 180 days
measure: Ultrasound congestion parameters by Venous Excess Ultrasound (VExUS) protocol
timeFrame: baseline - 30 days - 90 days - 180 days
measure: Congestion assessed by lung ultrasound
timeFrame: baseline - 30 days - 90 days - 180 days
measure: Quality of life status
timeFrame: baseline - 30 days - 90 days - 180 days
measure: 6 minute walk test
timeFrame: baseline - 30 days - 90 days - 180 days
Other outcomes:
Locations:
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
state: Córdoba (Andalucía)
Study officials:
affiliation: Hospital Universitario Reina Sofía de Córdoba
name: Alberto Torres Zamudio, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maimónides Biomedical Research Institute of Córdoba
name: Juan Carlos Castillo Domínguez, MD, PhD
role: STUDY_DIRECTOR
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