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

Maimónides Biomedical Research Institute of Córdoba

Status and phase

Completed

Phase 2

Conditions

Withdrawal

Dyspnea

Electric Impedance

Heart Failure

Safety

Treatments

Drug: Diuretics withdrawal

Drug: Diuretics maintenance

Study type

Interventional

Funder types

Other

Identifiers

NCT05964738

REDICAE

Details and patient eligibility

About

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.

Full 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)

Enrollment

98 patients

Sex

All

Ages

18+ years old

Volunteers

No 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