The Effects of Decreasing the Lasix Dose on the Cardiorenal System

NCT00982423 | Completed Phase 1 Results DMC

• 4 other identifiers: 09-003210R01HL084155P01HL076611UL1TR000135
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators' objective is to define the effects of decreasing the furosemide dose on heart, kidney and humoral function in people with compensated heart failure and kidney dysfunction and also in people with compensated heart failure without kidney dysfunction. Secondly, to define the humoral activation in both groups.

Conditions

Heart Failure; Kidney Dysfunction

Keywords

heart failure; heart failure with and without kidney dysfunction

Outcome Measures

Primary Outcomes (1)

• Renal Function as Measured by Glomerular Filtration Rate (GFR) at Baseline and in Response to Decreasing Furosemide Dose

  Kidney function was measured by GFR determined by iothalamate clearance. GFR describes the flow rate of filtered fluid through the kidney measured in milliliters per minute per 1.73 m\^2 of body surface area. A lower GFR means the kidney is not filtering normally. An estimated GFR of less than 60 mg/min/1.73 m\^2 of body surface area is considered to be impaired kidney function.

  3 weeks, approximately 6 weeks

Secondary Outcomes (5)

• Renal Plasma Flow at Baseline and in Response to Decreasing Furosemide Dose

  3 weeks, approximately 6 weeks

• Aldosterone at Baseline and in Response to Decreasing Furosemide Dose

  3 weeks, approximately 6 weeks

• Plasma Renin Activity at Baseline and in Response to Decreasing Furosemide Dose

  3 weeks, approximately 6 weeks

• Angiotensin II at Baseline and in Response to Decreasing Furosemide Dose

  3 weeks, approximately 6 weeks

• Plasma Cyclic Guanosine Monophosphate (cGMP) at Baseline and in Response to Decreasing Furosemide Dose

  3 weeks, approximately 6 weeks

Study Arms (1)

Furosemide

EXPERIMENTAL

Subjects received their clinically prescribed dose of furosemide for a 3 week stabilization period, then were assessed for cardiorenal and humoral function. Subjects then had a 50% reduction of the furosemide dose for a 3 week stabilization period, and were assessed for cardiorenal and humoral function again.

Drug: Furosemide

Interventions

Furosemide DRUG

Subjects received their clinically prescribed dose of furosemide for a 3 week stabilization period, then were assessed for cardiorenal and humoral function. Subjects then had a 50% reduction of the furosemide dose for a 3 week stabilization period, and were assessed for cardiorenal and humoral function again.

Also known as: Lasix

Furosemide

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Left ventricular ejection fraction of equal or less than 40% assessed by echocardiography, nuclear scan, MRI, or left ventriculogram within the past 36 months.
• Stable New York Heart Association (NYHA) class II and III symptoms as defined by: a) no change in NYHA symptoms over the past 3 months; b) on stable doses of ACE inhibitor or beta blocker or digoxin or furosemide or angiotensin II receptor, type 1 (AT1) blocker over the past 3 months; c) no episode of decompensated CHF over the past 6 months.
• Calculated creatinine clearance of equal or less than 80 ml/min, using the Cockcroft-Gault formula assessed within the past 36 months and a confirmatory calculated creatinine clearance equal or less than 80 ml/min at the time of enrollment.
• Left ventricular ejection fraction of equal or less than 40% assessed by echocardiography, nuclear scan or left ventriculogram within the past 36 months.
• Stable New York Heart Association (NYHA) class II and III symptoms as defined by: a) no change in NYHA symptoms over the past 3 months; b) on stable doses of ACE inhibitor or beta blocker or digoxin or furosemide or AT1 blocker over the past 3 months; c) no episode of decompensated CHF over the past 6 months.
• Calculated creatinine clearance of equal or less than 60 ml/min and greater than 20 ml/min, using the Cockcroft-Gault formula assessed within the past 36 months and a confirmatory calculated creatinine clearance equal or less than 60 ml/min and greater than 20 ml/min at the time of enrollment.

You may not qualify if:

• Prior diagnosis of intrinsic renal diseases including renal artery stenosis of \> 50%
• Peritoneal or hemodialysis within 90 days or anticipation that dialysis or ultrafiltration of any form will be required during the study period
• Patients who are taking aldosterone antagonist
• Hospitalization for decompensated CHF during the past 6 months
• Subjects on other diuretics besides furosemide
• Myocardial infarction within 6 months of screening
• Unstable angina within 6 months of screening or any evidence of myocardial ischemia
• Significant valvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis
• Severe congenital heart diseases
• Sustained ventricular tachycardia or ventricular fibrillation within 14 days of screening
• Second or third degree heart block without a permanent cardiac pacemaker
• Stroke within 3 months of screening or other evidence of significantly compromised central nervous system (CNS) perfusion
• Alanine Aminotransferase (ALT) result \>1.5 times the upper limit of normal
• Serum sodium of \< 125 milliequivalent (mEq)/dL or \> 150 mEq/dL
• Serum potassium of \< 3.5 mEq/dL or \> 5.5 mEq/dL

Sponsors & Collaborators

• Mayo Clinic: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• McKie PM, Schirger JA, Benike SL, Harstad LK, Chen HH. The effects of dose reduction of furosemide on glomerular filtration rate in stable systolic heart failure. JACC Heart Fail. 2014 Dec;2(6):675-7. doi: 10.1016/j.jchf.2014.05.014. Epub 2014 Sep 24. No abstract available.

  PMID: 25262369 RESULT

MeSH Terms

Conditions

Heart Failure

Interventions

Furosemide

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds

Results Point of Contact

• Title: Dr. Horng Chen
• Organization: Mayo Clinic

chen.horng@mayo.edu

507-538-2354

Study Officials

• Horng H Chen, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PI

Study Record Dates

• First Submitted: September 18, 2009
• First Posted: September 23, 2009
• Study Start: July 1, 2009
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: July 20, 2015
• Results First Posted: July 20, 2015

Record last verified: 2015-06

Locations

US (1)