A Comparison of Hydrochlorothiazide and Metolazone in Combination With Furosemide in Congestive Heart Failure Patients

Congestive Heart Failure Clinical Trial

Official title: A Comparison of Hydrochlorothiazide and Metolazone in Combination With Furosemide in Congestive Heart Failure Patients

Status Recruiting

Clinical Trial Summary

The purpose of this research study is to compare the effectiveness of hydrochlorothiazide or metolazone in combination with furosemide. Patients with heart failure suffer from swelling because of too much fluid in the body. Furosemide, hydrochlorothiazide, and metolazone are all water pills used to treat the swelling. For most patients, taking furosemide alone is successful. However, sometimes patients need to add another water pill. Doctors usually add either metolazone or hydrochlorothiazide. It is not clear which water pill is better when added to furosemide. The purpose of this study is to determine which water pill when added to furosemide is the best at reducing excess fluid in the body.

Clinical Trial Description

Objective: To establish which combination of diuretics is the most effective in promoting diuresis in congestive heart failure patients. Secondary Objectives: To determine the duration of action of furosemide as monotherapy and in combination with either hydrochlorothiazide or metolazone. To determine the effect of diuretic combination therapy on neurohormonal activation. Background: Diuretic resistance occurs when a potent diuretic drug, such as furosemide, is given in therapeutic doses and fails to reduce extracellular fluid volume to the desired level in an edematous patient. Studies have shown that metolazone and hydrochlorothiazide have demonstrated a synergistic response when used in combination with furosemide in congestive heart failure patients. The current guidelines for treating diuretic resistance in congestive heart failure patients recommend the metolazone-furosemide combination. However, there is no evidence to conclude that this combination is superior to hydrochlorothiazide-furosemide in increasing diuresis. Methods: Randomized, double-blind, crossover study to compare the efficacy of hydrochlorothiazide and metolazone in combination with stable doses of furosemide in 13 patients with congestive heart failure. The primary endpoint will be change in urinary output. Secondary endpoints will be changes in weight, neurohormones (angiotensin II, catecholamines, brain natriuretic peptide, aldosterone), and electrocardiographic parameters of ventricular instability. Study procedures will be performed at the UNM General Clinical Research Center. Patients will be hospitalized for 2 separate 4-day admissions, separated by a 1-week washout period. At each admission each patient will receive furosemide in combination with either metolazone or hydrochlorothiazide (metolazone for one admission and hydrochlorothiazide for the other). Following administration of combination therapy, blood and urine samples will be collected throughout the day to chart the onset and magnitude of effect of each treatment regimen. Various hemodynamic, renal, endocrine, and neurohormonal parameters will be assesed as will the effect of each combination treatment on ventricular instability using 12-lead electrocardiography. Data will be analyzed using ANOVA to compare changes from baseline and the Student t-test to analyze intertreatment differences.

All statistical analysis will be performed using SAS v6.12. ;

Study Design

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

Related Conditions & MeSH terms

• Congestive Heart Failure
• Heart Failure

• NCT number: NCT00690521
• Study type: Interventional
• Source: University of New Mexico
• Contact: Joe R. Anderson, PharmD
• Phone: 505-272-3664
• Email: janderson@salud.unm.edu
• Status: Recruiting
• Phase: Phase 4
• Start date: January 2003
• Completion date: January 2009