Bumetanide Versus Furosemide in Heart Failure
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, 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|
- Insulin resistance, as determined by frequently sampled intravenous glucose tolerance test with minimal model analysis (FSIGT MINMOD) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- Fasting blood glucose [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- Glycosylated hemoglobin (HbA1c) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- Serum creatinine, sodium, potassium, and chloride [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
- Submaximal exercise capacity as determined by the 6-minute walk test [ Time Frame: 3 months ] [ Designated as safety issue: No ]
- New York Heart Association Function Class heart failure (NYHA FC) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
|Study Start Date:||January 2011|
|Estimated Study Completion Date:||June 2013|
|Estimated Primary Completion Date:||January 2013 (Final data collection date for primary outcome measure)|
Active Comparator: Furosemide
Patients will be assigned to furosemide therapy (20mg to 80mg) orally, once or twice daily for an 8-week period.
Current dose of furosemide will be maintained and equivalent dose bumetanide will be used following crossover
Other Name: LasixDrug: 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.
Equivalent dose to pre-existing furosemide will be used
Other Names:Drug: bumetanide
0.5mg to 2mg orally once or twice daily
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00372762
|University Hospital, London Health Sciences Centre|
|London, Ontario, Canada, N6A 5A5|
|Principal Investigator:||Neville G Suskin, MBChB, MSc||LHSC, University of Western Ontario|