Clinical trial NCT00372762: Bumetanide Versus Furosemide in Heart Failure
Official title: Bumetanide Has a More Favourable Effect on Insulin Resistance Than Furosemide in Patients With Heart Failure - A Pilot Study
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Heart Failure
Keywords: Insulin resistance
heart failure
diuretic therapy
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: University of Western Ontario, Canada
First posted: 2006-09-07
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Eligibility 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)

Primary outcomes:
measure: Insulin resistance, as determined by frequently sampled intravenous glucose tolerance test with minimal model analysis (FSIGT MINMOD)
timeFrame: 3 months
Secondary outcomes:
measure: Fasting blood glucose
timeFrame: 3 months
measure: Glycosylated hemoglobin (HbA1c)
timeFrame: 3 months
measure: Serum creatinine, sodium, potassium, and chloride
timeFrame: 3 months
measure: Submaximal exercise capacity as determined by the 6-minute walk test
timeFrame: 3 months
measure: New York Heart Association Function Class heart failure (NYHA FC)
timeFrame: 3 months
Other outcomes:
Locations:
city: London
country: Canada
facility: University Hospital, London Health Sciences Centre
state: Ontario
Study officials:
affiliation: LHSC, University of Western Ontario
name: Neville G Suskin, MBChB, MSc
role: PRINCIPAL_INVESTIGATOR
References: