Bumetanide Versus Furosemide in Heart Failure

This study has been withdrawn prior to enrollment.
(Due to changes within the research program this study is not feasible at this time)
Sponsor:
Collaborator:
University of Western Ontario, Canada
Information provided by (Responsible Party):
Neville Suskin, Lawson Health Research Institute
ClinicalTrials.gov Identifier:
NCT00372762
First received: September 6, 2006
Last updated: March 26, 2014
Last verified: March 2014

September 6, 2006
March 26, 2014
January 2011
January 2013   (final data collection date for primary outcome measure)
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 ]
Insulin resistance, as determined by frequently sampled intravenous glucose tolerance test with minimal model analysis (FSIGT MINMOD)
Complete list of historical versions of study NCT00372762 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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)
Not Provided
Not Provided
 
Bumetanide Versus Furosemide in Heart Failure
Bumetanide Has a More Favourable Effect on Insulin Resistance Than Furosemide in Patients With Heart Failure - A Pilot Study

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Heart Failure
  • Drug: Furosemide
    Current dose of furosemide will be maintained and equivalent dose bumetanide will be used following crossover
    Other Name: Lasix
  • Drug: Bumetanide
    Equivalent dose to pre-existing furosemide will be used
    Other Names:
    • Bumex
    • Burinex
  • Drug: furosemide
    20mg to 80mg orally once or twice daily
    Other Name: Lasix
  • Drug: bumetanide
    0.5mg to 2mg orally once or twice daily
    Other Names:
    • Bumex
    • Burinex
  • Active Comparator: Furosemide
    Patients will be assigned to furosemide therapy (20mg to 80mg) orally, once or twice daily for an 8-week period.
    Interventions:
    • Drug: Furosemide
    • Drug: furosemide
  • 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.
    Interventions:
    • Drug: Bumetanide
    • Drug: bumetanide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Withdrawn
0
June 2013
January 2013   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00372762
R-06-415
No
Neville Suskin, Lawson Health Research Institute
Lawson Health Research Institute
University of Western Ontario, Canada
Principal Investigator: Neville G Suskin, MBChB, MSc LHSC, University of Western Ontario
Lawson Health Research Institute
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP