Bumetanide Versus Furosemide in Heart Failure

Study Description

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Brief Summary:

Patients with NYHA FC II-III heart failure will be randomized in a cross-over fashion to 8 weeks of bumetanide versus furosemide therapy (equipotent dose), to test whether bumetanide therapy has a superior effect on insulin resistance compared to furosemide. Patients will be subject to a frequently sampled intravenous glucose tolerance test (FSIGT) with minimal model (MINMOD) analysis to assess insulin resistance and to a 6-minute walk test (6MWT) to assess functional capacity; patient recruitment and retention success, as well as medication adherence, will also be assessed.

Condition or disease	Intervention/treatment	Phase
Heart Failure	Drug: Furosemide; Drug: Bumetanide; Drug: furosemide; Drug: bumetanide	Phase 3

Detailed Description:

Insulin resistance is common in patients with heart failure (HF) and is associated with a worse functional capacity and more severe symptoms of heart failure. The majority of HF patients take furosemide on at least a daily basis for symptom relief. Bumetanide is a loop diuretic with a similar therapeutic diuretic effect to furosemide. There is evidence from observational and small comparative trials that bumetanide has a significantly less deleterious effect on indirect measures of insulin resistance compared with furosemide. However, a formal comparison between the 2 drugs using rigorous measures of insulin resistance has never been conducted in patients with HF. If bumetanide can be demonstrated to have a similar diuretic and a superior (less deleterious) effect on insulin resistance in patients with HF, the potential exists for bumetanide to have a significantly reduced morbidity in patients with heart failure compared to furosemide. In order to prepare for such a study, the variance of the MINMOD-derived insulin resistance from the FSIGT (26), in this group of patient needs to be determined along with the feasibility of conducting such a study. Functional capacity will be determined by duplicate 6-minute walk tests.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	0 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Bumetanide Has a More Favourable Effect on Insulin Resistance Than Furosemide in Patients With Heart Failure - A Pilot Study
Study Start Date :	January 2011
Estimated Primary Completion Date :	January 2013
Estimated Study Completion Date :	June 2013

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: Furosemide; Patients will be assigned to furosemide therapy (20mg to 80mg) orally, once or twice daily for an 8-week period.	Drug: Furosemide; Current dose of furosemide will be maintained and equivalent dose bumetanide will be used following crossover; Other Name: Lasix Drug: furosemide; 20mg to 80mg orally once or twice daily; Other Name: Lasix
Active Comparator: Bumetanide; Patients will be assigned to bumetanide therapy at an equipotent dose to furosemide therapy (1mg bumetanide is equivalent to 40mg furosemide)for an 8-week period.	Drug: Bumetanide; Equivalent dose to pre-existing furosemide will be used; Other Names: Bumex; Burinex Drug: bumetanide; 0.5mg to 2mg orally once or twice daily; Other Names: Bumex; Burinex

Outcome Measures

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Primary Outcome Measures :

1. Insulin resistance, as determined by frequently sampled intravenous glucose tolerance test with minimal model analysis (FSIGT MINMOD) [ Time Frame: 3 months ]

Secondary Outcome Measures :

1. Fasting blood glucose [ Time Frame: 3 months ]
2. Glycosylated hemoglobin (HbA1c) [ Time Frame: 3 months ]
3. Serum creatinine, sodium, potassium, and chloride [ Time Frame: 3 months ]
4. Submaximal exercise capacity as determined by the 6-minute walk test [ Time Frame: 3 months ]
5. New York Heart Association Function Class heart failure (NYHA FC) [ Time Frame: 3 months ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Men and women ≥18 years of age
2. NHYA FC II or III HF AND documented LVEF ≤40% within 6 months prior to study entry
3. Taking 20 mg to 80 mg furosemide orally once or twice per day
4. No changes to cardiac medications for 3 months prior to study entry and no anticipated changes of medications for the duration of the study
5. No changes to oral anti-diabetic medications (if applicable) for 3 months prior to study entry, and no anticipated changes for the duration of the study (metformin, sulphonylurea type, glitazone type)
6. Ability to provide written consent

Exclusion Criteria:

1. Known sensitivity to bumetanide
2. Myocardial infarction, coronary angioplasty, coronary artery bypass surgery, admission for HF or unstable angina within a 3 month period prior to study recruitment
3. Planned coronary intervention within 6 months
4. Patients who are taking insulin
5. Patients with chronic renal (serum creatinine ≥ 200 μmol/L) or hepatic impairment (known cirrhosis or AST or ALT > 1.5 x upper limit of normal)

Contacts and Locations

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Locations

Canada, Ontario
University Hospital, London Health Sciences Centre
London, Ontario, Canada, N6A 5A5

Sponsors and Collaborators

Lawson Health Research Institute

University of Western Ontario, Canada

Investigators

Principal Investigator:	Neville G Suskin, MBChB, MSc	LHSC, University of Western Ontario

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Neville Suskin, Principal Investigator, Lawson Health Research Institute
ClinicalTrials.gov Identifier:	NCT00372762 History of Changes
Other Study ID Numbers:	R-06-415
First Posted:	September 7, 2006
Last Update Posted:	March 27, 2014
Last Verified:	March 2014

Keywords provided by Neville Suskin, Lawson Health Research Institute:

Insulin resistance; heart failure; diuretic therapy

Additional relevant MeSH terms:

Heart Failure; Insulin Resistance; Heart Diseases; Cardiovascular Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Furosemide	Bumetanide; Diuretics; Natriuretic Agents; Physiological Effects of Drugs; Sodium Potassium Chloride Symporter Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action