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

NCT ID: NCT00690521

Last Updated: 2024-10-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-10-26
• Study Completion Date: 2009-11-10

Brief Summary

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

Conditions

Congestive Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Furosemide and hydrochlorothiazide

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.

Group Type: EXPERIMENTAL

Treatment of Furosemide + Hydrochlorothiazide

Intervention Type: 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.

Furosemide and metolazone

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.

Group Type: EXPERIMENTAL

Treatment of Furosemide + Metolazone

Intervention Type: 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.

Interventions

Treatment of Furosemide + Hydrochlorothiazide

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.

Intervention Type: DRUG

Treatment of Furosemide + Metolazone

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.

Intervention Type: DRUG

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 98 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of New Mexico

OTHER

Sponsor Role: lead

Responsible Party

Joe R. Anderson

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University Of New Mexico Hospital

Albuquerque, New Mexico, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

HRRC 03-477

Identifier Type: -

Identifier Source: org_study_id