Bumetanide vs. Furosemide in Heart Failure

Condition(s) targeted: Heart Failure

Intervention: Furosemide (Drug); Bumetanide (Drug); furosemide (Drug); bumetanide (Drug)

Phase: Phase 3

Status: Not yet recruiting

Sponsored by: Lawson Health Research Institute

Official(s) and/or principal investigator(s):
Neville Suskin, MBChB, etc, Principal Investigator, Affiliation: LHSC, University of Western Ontario

Overall contact:
Neville Suskin, MBChB, etc, Phone: (519) 685-8300, Ext: 33488, Email: neville.suskin@lhsc.on.ca

Patients with NYHA FC II-III heart failure will be randomized in a cross-over fashion to 8 weeks of bumetanide vs. 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.

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

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Crossover Assignment, Efficacy Study

Primary outcome: Insulin resistance, as determined by frequently sampled intravenous glucose tolerance test with minimal model analysis (FSIGT MINMOD)

Secondary outcome:

Fasting blood glucose

Glycosylated hemoglobin (HbA1c)

Serum creatinine, sodium, potassium, and chloride

Submaximal exercise capacity as determined by the 6-minute walk test

New York Heart Association Function Class heart failure (NYHA FC)

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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)

Neville Suskin, MBChB, etc, Phone: (519) 685-8300, Ext: 33488, Email: neville.suskin@lhsc.on.ca

University Hospital, London Health Sciences Centre, London, Ontario N6A 5W9, Canada

Starting date: September 2009
Ending date: December 2010
Last updated: July 8, 2009