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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
98
Diuretics that not have been demonstrated improve survival in chronic HFrEF are withdrawn
Any diuretic could be used
Hospital Universitario Reina Sofía
Córdoba, Córdoba (Andalucía), Spain
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.
Time frame: baseline - 30 days - 90 days - 180 days
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.
Time frame: 180 days
Variation of plasmatic levels of natriuretic peptides
Levels of the N-terminal pro b-type natriuretic peptide (NT-proBNP)
Time frame: baseline - 30 days - 90 days - 180 days
Tissue fluid overload
Variation of plasmatic levels of antigen carbohydrate 125 (CA-125)
Time frame: baseline - 30 days - 90 days - 180 days
Body Composition Monitor (BCM) of Fresenius Medical Care
Variation of fluid overload assessed by bioelectrical impedance analysis
Time frame: baseline - 30 days - 90 days - 180 days
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.
Time frame: baseline - 30 days - 90 days - 180 days
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)
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Time frame: baseline - 30 days - 90 days - 180 days
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%.
Time frame: baseline - 30 days - 90 days - 180 days
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)
Time frame: baseline - 30 days - 90 days - 180 days
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
Time frame: baseline - 30 days - 90 days - 180 days
Congestion assessed by lung ultrasound
Pleural effusion or pathological B lines. More than two B lines are considered as pathological.
Time frame: baseline - 30 days - 90 days - 180 days
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.
Time frame: baseline - 30 days - 90 days - 180 days
6 minute walk test
Change From Baseline in meters walked, as assessed by the 6 minute walk test
Time frame: baseline - 30 days - 90 days - 180 days