Bumetanide Versus Furosemide in Heart Failure

• ClinicalTrials.gov Identifier: NCT00372762
• Recruitment Status: Withdrawn
• First Posted: September 7, 2006
• Last Update Posted: March 27, 2014
• Sponsor: Lawson Health Research Institute
• Collaborator: University of Western Ontario, Canada
• Information provided by (Responsible Party): Neville Suskin, Lawson Health Research Institute

Study Description

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

• 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

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

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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• 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

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

• Responsible Party: Neville Suskin, Principal Investigator, Lawson Health Research Institute
• ClinicalTrials.gov Identifier: NCT00372762
• 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; Heart Diseases; Cardiovascular Diseases; Furosemide; Bumetanide; Diuretics; Natriuretic Agents; Physiological Effects of Drugs; Sodium Potassium Chloride Symporter Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action