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

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 hydrochlorothiazide with 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: Study to compare the efficacy of hydrochlorothiazide with 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.d

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Congestive Heart Failure Cardiovascular Diseases Heart Diseases Heart Failure

Age range

18 year–98 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

University Of New Mexico Hospital

Albuquerque, New Mexico, 87120, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Age >18 years
Diagnosis of chronic congestive heart failure with an ejection fraction ≤45%
Currently on a stable regimen of furosemide consisting of a daily dose of at least 80 mg for at least two weeks.
Patients receiving ACE-inhibitors and/or beta-blockers must be taking these medications for at least two weeks in stable doses.

Exclusion criteria

Renal dysfunction (serum creatinine >2 mg/dl or creatinine clearance of <30 ml/min as calculated by the Cockroft and Gault equation)
Hepatic dysfunction (AST and ALT >3 times the upper limit of the normal)
Hypokalemia (<4.0 mg/dl)
Concomitant treatment with any diuretic other than furosemide (with the exception of spironolactone).

Treatment and study plan

Treatment of Furosemide + Hydrochlorothiazide

Drug

A randomized, double-blind, crossover study designed to compare the efficacy of hydrochlorothiazide in combination with stable doses of furosemide in congestive heart failure patients.

Treatment of Furosemide + Metolazone

Drug

A randomized, double-blind, crossover study designed to compare the efficacy of metolazone in combination with stable doses of furosemide in congestive heart failure patients.

Primary outcomes

Participants With Change in Urinary Output

Time frame: First Intervention (4 days), Washout (7 days), and Second Intervention (4 days)

Sponsors and collaborators

Lead sponsor

University of New Mexico

Other

Registry information

Important dates

Study start: 2004
Primary completion: 2009
Study completion: 2009
First posted: Jun 4, 2008
Registry last updated: Oct 10, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed