The Effects of Decreasing the Lasix Dose on the Cardiorenal System

NCT ID: NCT00982423

Last Updated: 2015-07-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2014-07-31

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.

Detailed Description

The broad objective of this protocol is to advance our understanding of the pathophysiological mechanisms of human Cardiorenal Syndrome (CRS) with a specific emphasis upon the biological interaction between diuretic therapy, the renin-angiotensin-aldosterone-system (RAAS) and cyclic 3'-5'-guanosine monophosphate (cGMP) pathway.

Conditions

Heart Failure; Kidney Dysfunction

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Furosemide

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.

Group Type: EXPERIMENTAL

Furosemide

Intervention Type: 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.

Interventions

Furosemide

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.

Intervention Type: DRUG

Other Intervention Names

Lasix

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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
• Serum digoxin level of > 2.0 ng/ml
• Hemoglobin < 10 gm/dl
• Other acute or chronic medical conditions or laboratory abnormality which may increase the risks associated with study participation or may interfere with interpretation of the data
• Received an investigational drug within 1 month prior to dosing
• Patients with an allergy to iodine.
• Female subject who is pregnant or breastfeeding
• In the opinion of the investigator is unlikely to comply with the study protocol or is unsuitable for any reason.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Horng Chen

MD, PI

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Horng H Chen, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 25262369 (View on PubMed)

Other Identifiers

R01HL084155

Identifier Type: NIH

Identifier Source: secondary_id

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P01HL076611

Identifier Type: NIH

Identifier Source: secondary_id

View Link

UL1TR000135

Identifier Type: NIH

Identifier Source: secondary_id

View Link

09-003210

Identifier Type: -

Identifier Source: org_study_id