Bumetanide Versus Furosemide in Heart Failure

Sponsor

Lawson Health Research Institute (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00372762

Collaborator

University of Western Ontario, Canada (Other)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

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

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 :

Jan 1, 2011

Anticipated Primary Completion Date :

Jan 1, 2013

Anticipated Study Completion Date :

Jun 1, 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 Names: Lasix Drug: furosemide 20mg to 80mg orally once or twice daily Other Names: 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

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 Names:

Lasix

Drug: furosemide

20mg to 80mg orally once or twice daily

Other Names:

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

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men and women ≥18 years of age
NHYA FC II or III HF AND documented LVEF ≤40% within 6 months prior to study entry
Taking 20 mg to 80 mg furosemide orally once or twice per day
No changes to cardiac medications for 3 months prior to study entry and no anticipated changes of medications for the duration of the study
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)
Ability to provide written consent

Exclusion Criteria:

Known sensitivity to bumetanide
Myocardial infarction, coronary angioplasty, coronary artery bypass surgery, admission for HF or unstable angina within a 3 month period prior to study recruitment
Planned coronary intervention within 6 months
Patients who are taking insulin
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)