Effect of Furosemide Withdraw in Stable Chronic Heart Failure Outpatients
- Registration Number
- NCT02689180
- Lead Sponsor
- Hospital de Clinicas de Porto Alegre
- Brief Summary
The ReBIC-1 trial was designed to evaluate the potential clinical risks and benefits of withdrawing furosemide use in stable, apparently euvolemic, chronic HF outpatients in a multicentric double-blinded randomized clinical trial.
- Detailed Description
Diuretics play a central role in HF treatment, particularly during episodes of acute decompensation. Furosemide is the prototype of loop diuretics, acting through the inhibition of the Na+K+2Cl- pump at the thick ascending limb of the Henle loop. According to international registries, almost all patients receive a loop diuretic during a hospital stay for acute decompensated HF and the majority are discharged taking a "maintenance dose". Despite the undeniable beneficial hemodynamic effects of improvement of peripheral and central congestion, the net clinical effect of the chronic use of diuretics on HF prognosis is controversial.
Observational studies suggest that use of high doses of diuretics might be related to unfavorable clinical consequences. Undesirable side effects of loop diuretics are not trivial and involve activation of the renin-angiotensin-aldosterone system, elevation of norepinephrine levels, increases in heart rate, detrimental effects on renal function and several electrolyte disturbances.
Few prospective clinical studies, however, directly evaluated the clinical risks and benefits of diuretics. Most of these studies were under-powered, performed more than 2 decades ago, before modern HF therapy with current drugs and devices was completely implemented.
Current clinical guidelines are unanimous to recommend use of diuretics in HF patients with clinical signs and symptoms of congestion, but reinforce the lack of solid clinical scientific evidence for its use, and the potential risks that might be involved. The European Society of Cardiology proposes the administration of the lowest dose necessary to achieve euvolemia, avoiding the unnecessary delay in the use of drugs that modify the natural history of the disease.
Based on these uncertainties about diuretic use in HF, the ReBIC-1 trial was designed to evaluate the potential clinical risks and benefits of withdrawing furosemide use in stable, apparently euvolemic, chronic HF outpatients in a multicentric double-blinded randomized clinical trial.
ReBIC is a Brazilian research network created to develop clinical studies in heart failure and composed predominantly by university tertiary care hospitals. ReBIC and the ReBIC-1 trial were sponsored by the Brazilian National Council for Scientific and Technological Development (CNPq, Brazil), a public governmental institution. Data collection, management, and analysis were performed at the network's data coordinating center at Hospital de Clínicas de Porto Alegre. All the authors reviewed and approved the manuscript and assume full responsibility for the accuracy and completeness of the data and for the fidelity of this report of the study protocol.
ReBIC-1 is a randomized, double-blind, parallel group, placebo-controlled, two-arm trial comparing the short-term efficacy and safety of discontinuation of furosemide in apparently euvolemic outpatients with chronic stable HF and reduced left ventricular ejection fraction (HF-REF).
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 230
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Withdraw of furosemide Placebo Withdraw of of 40 or 80 mg of furosemide per day Maintenance of furosemide Furosemide Maintenance of 40 or 80 mg of furosemide per day
- Primary Outcome Measures
Name Time Method Feasibility of furosemide withdraw - proportion of patients maintained without diuretic during follow-up 90 days Proportion of patients maintained without diuretic during follow-up
Safety of furosemide withdraw - dyspnea score variation assessed by a visual analog scale 90 days Dyspnea score variation assessed by a visual analog scale after randomization
- Secondary Outcome Measures
Name Time Method Variation in meters walked assessed by the 6 minute walking test Baseline and 90 days Variation in renal function Baseline, 15, 45 and 90 days Change in glomerular filtration rate ( ml/min /1.73 m²) estimated by the Modification of Diet in Renal Disease equation ( MDRD)
Variation of plasmatic levels of natriuretic peptides Baseline and 90 days Levels of the N-terminal brain natriuretic peptide (NT pro-BNP)
Variation on the Clinical Congestion Score Baseline, 15, 45 and 90 days Clinical congestion score assessed by clinical history and physical examination (score from 1 to 22 point)
Clinical composite endpoints 90 days Hospital admissions, emergency room visits and death within 90 days
Trial Locations
- Locations (1)
Cardiovascular Division, Hospital de Clínicas de Porto Alegre
🇧🇷Porto Alegre, RS, Brazil