The Effects of Decreasing the Lasix Dose on the Cardiorenal System

Mayo Clinic41 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Heart Failure Kidney Dysfunction

Interventions

FurosemideDRUG

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 Years

Medical Language ↔ Plain English

Inclusion Criteria for Subjects with Compensated CHF without Renal Dysfunction: * 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. Inclusion Criteria for Subjects with Compensated CHF with Renal Dysfunction: * 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 for both groups: * 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.

Locations (1)

Mayo Clinic

Rochester, Minnesota, United States

Outcomes

Primary Outcomes

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.

Time frame: 3 weeks, approximately 6 weeks

Secondary Outcomes

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

Effective renal plasma flow (eRPF) is a measure used to calculate renal plasma flow (RPF) and hence estimate renal function. Renal plasma flow is the volume of blood plasma that flows through the kidneys per unit time, measured as ml/min.

Time frame: 3 weeks, approximately 6 weeks

Aldosterone at Baseline and in Response to Decreasing Furosemide Dose

Aldosterone is part of the renin-angiotensin-aldosterone system (RAAS). Drugs that interfere with the secretion or action of aldosterone are in use as antihypertensives, like lisinopril, which lowers blood pressure by blocking the angiotensin-converting enzyme (ACE), leading to lower aldosterone secretion. The net effect of these drugs is to reduce sodium and water retention but increase retention of potassium.

Time frame: 3 weeks, approximately 6 weeks

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

Plasma renin activity is a measure of the activity of the plasma enzyme renin, which plays a major role in the body's regulation of blood pressure, thirst, and urine output. Renin is an enzyme that hydrolyses angiotensinogen secreted from the liver into the peptide angiotensin I. Renin's primary function is to cause an increase in blood pressure, leading to restoration of perfusion pressure in the kidneys.

Time frame: 3 weeks, approximately 6 weeks

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.