Bumetanide Versus Furosemide in Heart Failure

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Bumetanide Has a More Favourable Effect on Insulin Resistance Than Furosemide in Patients With Heart Failure - A Pilot Study

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Furosemide
* Drug: Bumetanide
* Drug: furosemide
* Drug: bumetanide


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Furosemide<br>Patients will be assigned to furosemide therapy (20mg to 80mg) orally, once or twice daily for an 8-week period. | Drug: Furosemide<br>* Current dose of furosemide will be maintained and equivalent dose bumetanide will be used following crossover<br>* Other names: Lasix;Drug: furosemide<br>* 20mg to 80mg orally once or twice daily<br>* Other names: Lasix;|
| Active Comparator: Bumetanide<br>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<br>* Equivalent dose to pre-existing furosemide will be used<br>* Other names: Burinex;Drug: bumetanide<br>* 0.5mg to 2mg orally once or twice daily<br>* Other names: Burinex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin resistance, as determined by frequently sampled intravenous glucose tolerance test with minimal model analysis (FSIGT MINMOD) |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin resistance, heart failure, diuretic therapy