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Effect of Furosemide Withdraw in Stable Chronic Heart Failure Outpatients (ReBIC-1)

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ClinicalTrials.gov Identifier: NCT02689180
Recruitment Status : Unknown
Verified February 2016 by Hospital de Clinicas de Porto Alegre.
Recruitment status was:  Recruiting
First Posted : February 23, 2016
Last Update Posted : February 23, 2016
Sponsor:
Collaborator:
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Heart Failure Drug: Placebo Drug: Furosemide Phase 3

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).


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 230 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Furosemide Withdraw in Stable Chronic Heart Failure Outpatients With Left Ventricular Dysfunction - the Brazilian Research Network on Heart Failure
Study Start Date : May 2015
Estimated Primary Completion Date : May 2017
Estimated Study Completion Date : July 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure
Drug Information available for: Furosemide

Arm Intervention/treatment
Placebo Comparator: Withdraw of furosemide
Withdraw of of 40 or 80 mg of furosemide per day
Drug: Placebo
Replacement of furosemide by placebo

Active Comparator: Maintenance of furosemide
Maintenance of 40 or 80 mg of furosemide per day
Drug: Furosemide
Maintenance of furosemide on usual doses




Primary Outcome Measures :
  1. Feasibility of furosemide withdraw - proportion of patients maintained without diuretic during follow-up [ Time Frame: 90 days ]
    Proportion of patients maintained without diuretic during follow-up

  2. Safety of furosemide withdraw - dyspnea score variation assessed by a visual analog scale [ Time Frame: 90 days ]
    Dyspnea score variation assessed by a visual analog scale after randomization


Secondary Outcome Measures :
  1. Variation of plasmatic levels of natriuretic peptides [ Time Frame: Baseline and 90 days ]
    Levels of the N-terminal brain natriuretic peptide (NT pro-BNP)

  2. Variation in meters walked assessed by the 6 minute walking test [ Time Frame: Baseline and 90 days ]
  3. Variation in renal function [ Time Frame: 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)

  4. Variation on the Clinical Congestion Score [ Time Frame: Baseline, 15, 45 and 90 days ]
    Clinical congestion score assessed by clinical history and physical examination (score from 1 to 22 point)

  5. Clinical composite endpoints [ Time Frame: 90 days ]
    Hospital admissions, emergency room visits and death within 90 days



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

The ReBIC-1 study will enroll HF outpatients that fulfill the following criteria:

  1. age equal or greater than 18 year-old;
  2. New York Heart Association functional class I or II;
  3. Left Ventricular Ejection Fraction ≤ 45% by transthoracic two-dimensional echocardiography performed within 3 months before the screening visit;
  4. no previous HF related hospitalization or visit to emergency room within 6 months before the screening visit;
  5. treatment with a stable dose of furosemide (40 or 80 mg per day) for at least 6 months before the screening visit;
  6. plasma potassium < 5 mg/dl within 3 months before the screening visit;
  7. optimal HF treatment with an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) and beta-blockers, unless contraindicated or not tolerated.

The ReBIC-1 study will exclude HF outpatients that fulfill the following criteria:

  1. a clinical congestion score (CCS) > 5 points;
  2. prior acute coronary syndrome, stroke or myocardial revascularization within 3 months before the screening visit;
  3. any severe valve heart disease (aortic, mitral or tricuspid);
  4. severe pulmonary disease (asthma, emphysema or fibrosis);
  5. severe hepatic failure or cirrhosis;
  6. end-stage acute or chronic renal disease (on hemodialysis);
  7. malignancy on active treatment;
  8. congenital heart disease;
  9. participation on any other interventional clinical research;
  10. inability to understand and sign informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02689180


Contacts
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Contact: Luis Eduardo Rohde, PHD 555133598843 lerohde@gmail.com
Contact: Priscila Raupp da Rosa, MD 555199127137 raupp.priscilamd@gmail.com

Locations
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Brazil
Cardiovascular Division, Hospital de Clínicas de Porto Alegre Recruiting
Porto Alegre, RS, Brazil, 90035-903
Contact: Luis Eduardo Rohde, PHD    55513359 8843    rohde.le@gmail.com   
Contact: Priscila Raupp da Rosa, MD    555199127137    raupp.priscilamd@gmail.com   
Sub-Investigator: Priscila Raupp da Rosa, MD         
Principal Investigator: Luis E. Rohde, MD         
Principal Investigator: Andreia Biolo, MD         
Sponsors and Collaborators
Hospital de Clinicas de Porto Alegre
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Investigators
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Study Chair: Luis Eduardo Rohde, PHD Hospital de Clínicas de Porto Alegre

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hospital de Clinicas de Porto Alegre
ClinicalTrials.gov Identifier: NCT02689180     History of Changes
Other Study ID Numbers: 15-240
First Posted: February 23, 2016    Key Record Dates
Last Update Posted: February 23, 2016
Last Verified: February 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Hospital de Clinicas de Porto Alegre:
heart failure
diuretics
furosemide
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases
Furosemide
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action