Bumetanide Versus Furosemide in Heart Failure

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00372762
• Other study ID #: R-06-415
• Status: Withdrawn
• Phase: Phase 3
• First received: September 6, 2006
• Last updated: March 26, 2014
• Start date: January 2011
• Est. completion date: June 2013

Study information

• Verified date: March 2014
• Source: Lawson Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Heart Failure
• Insulin Resistance

Intervention

Drug:
• Furosemide
Current dose of furosemide will be maintained and equivalent dose bumetanide will be used following crossover
• Bumetanide
Equivalent dose to pre-existing furosemide will be used
• furosemide
20mg to 80mg orally once or twice daily
• bumetanide
0.5mg to 2mg orally once or twice daily

Locations

Country	Name	City	State
Canada	University Hospital, London Health Sciences Centre	London	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Lawson Health Research Institute	University of Western Ontario, Canada

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin resistance, as determined by frequently sampled intravenous glucose tolerance test with minimal model analysis (FSIGT MINMOD)		3 months	No
Secondary	Fasting blood glucose		3 months	No
Secondary	Glycosylated hemoglobin (HbA1c)		3 months	No
Secondary	Serum creatinine, sodium, potassium, and chloride		3 months	Yes
Secondary	Submaximal exercise capacity as determined by the 6-minute walk test		3 months	No
Secondary	New York Heart Association Function Class heart failure (NYHA FC)		3 months	No