Rational and design of a randomized, double-blind, multicenter trial to evaluate the safety and tolerability of furosemide withdrawal in stable chronic outpatients with heart failure: The ReBIC-1 trial

Am Heart J. 2017 Dec:194:125-131. doi: 10.1016/j.ahj.2017.08.012. Epub 2017 Aug 24.

Abstract

Aims: Furosemide is commonly prescribed for symptom relief in heart failure (HF) patients. Although few data support the continuous use of loop diuretics in apparently euvolemic HF patients with mild symptoms, there is concern about safety of diuretic withdrawal in these patients. The ReBIC-1 trial was designed to evaluate the safety and tolerability of withdrawing furosemide in stable, euvolemic, chronic HF outpatients. This multicenter initiative is part of the Brazilian Research Network in Heart Failure (ReBIC) created to develop clinical studies in HF and composed predominantly by university tertiary care hospitals.

Methods: The ReBIC-1 trial is currently enrolling HF patients in NYHA functional class I-II, left ventricular ejection fraction ≤45%, without a HF-related hospital admission within the last 6 months, receiving a stable dose of furosemide (40 or 80 mg per day) for at least 6 months. Eligible patients will be randomized to maintain or withdraw furosemide in a double-blinded protocol. The trial has two co-primary outcomes: (1) dyspnea assessment using a visual-analogue scale evaluated at 4 time points and (2) the proportion of patients maintained without diuretics during the follow-up period. Total sample size was calculated to be 220 patients. Enrolled patients will be followed up to 90 days after randomization, and diuretic will be restarted if clinical deterioration or signs of congestion are detected. Pre-defined sub-group analysis based on NT-proBNP levels at baseline is planned.

Perspective: Evidence-based strategies aiming to simplify HF pharmacotherapy are needed in clinical practice. The ReBIC-1 trial will determine the safety of withdrawing furosemide in stable chronic HF patients.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Biomarkers / blood
  • Clinical Deterioration
  • Diuretics / administration & dosage
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Tolerance*
  • Female
  • Furosemide / administration & dosage*
  • Heart Failure / blood
  • Heart Failure / diagnosis
  • Heart Failure / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Outpatients*
  • Peptide Fragments / blood
  • Treatment Outcome

Substances

  • Biomarkers
  • Diuretics
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Furosemide