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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2008 by University of New Mexico.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
University of New Mexico
ClinicalTrials.gov Identifier:
NCT00690521
First received: June 2, 2008
Last updated: June 3, 2008
Last verified: June 2008
  Purpose

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.


Condition Intervention Phase
Congestive Heart Failure
Drug: metolazone or hydrochlorothiazide
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Comparison of Hydrochlorothiazide and Metolazone in Combination With Furosemide in Congestive Heart Failure Patients

Resource links provided by NLM:


Further study details as provided by University of New Mexico:

Primary Outcome Measures:
  • The primary endpoint will be change in urinary output. [ Time Frame: 4 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Secondary endpoints will be changes in weight, neurohormones (angiotensin II, catecholamines, brain natriuretic peptide, aldosterone), and electrocardiographic parameters of ventricular instability. [ Time Frame: 4 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 13
Study Start Date: January 2003
Estimated Study Completion Date: January 2009
Estimated Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Patients will be randomized to receive either metolazone or HCTZ in a randomized, double-blind, placebo controlled crossover trial. The patients will receive the alternative medication if The specific dose of hydrochlorothiazide will be determined by the individual's creatinine clearance. A creatinine clearance of 30-50 mL/min will indicate a dose of 50 mg per day. A creatinine clearance of > 50 mL/min will indicate a dose of 25 mg per day.5 If metolazone is added to their regimen, the specific dose will be determined using the equivalence ratio of 5 mg metolazone to 50 mg hydrochlorothiazide.
Drug: metolazone or hydrochlorothiazide
The specific dose of hydrochlorothiazide will be determined by the individual's creatinine clearance. A creatinine clearance of 30-50 mL/min will indicate a dose of 50 mg per day. A creatinine clearance of > 50 mL/min will indicate a dose of 25 mg per day.5 If metolazone is added to their regimen, the specific dose will be determined using the equivalence ratio of 5 mg metolazone to 50 mg hydrochlorothiazide.
Active Comparator: 2
Patients will be randomized to receive either metolazone or HCTZ in a randomized, double-blind, placebo controlled crossover trial. The patients will receive the alternative medication if The specific dose of hydrochlorothiazide will be determined by the individual's creatinine clearance. A creatinine clearance of 30-50 mL/min will indicate a dose of 50 mg per day. A creatinine clearance of > 50 mL/min will indicate a dose of 25 mg per day.5 If metolazone is added to their regimen, the specific dose will be determined using the equivalence ratio of 5 mg metolazone to 50 mg hydrochlorothiazide.
Drug: metolazone or hydrochlorothiazide
The specific dose of hydrochlorothiazide will be determined by the individual's creatinine clearance. A creatinine clearance of 30-50 mL/min will indicate a dose of 50 mg per day. A creatinine clearance of > 50 mL/min will indicate a dose of 25 mg per day.5 If metolazone is added to their regimen, the specific dose will be determined using the equivalence ratio of 5 mg metolazone to 50 mg hydrochlorothiazide.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00690521

Contacts
Contact: Joe R. Anderson, PharmD 505-272-3664 janderson@salud.unm.edu
Contact: James J Nawarskas, PharmD 505-272-0584 jnawarskas@salud.unm.edu

Locations
United States, New Mexico
University Of New Mexico Hospital Recruiting
Albququerque, New Mexico, United States, 87120
Contact: Joe R. Anderson, PharmD    505-272-3664    janderson@salud.unm.edu   
Contact: James J. Nawarskas, PharmD    505-272-0584    jnawarskas@salud.unm.edu   
Principal Investigator: Joe R. Anderson, PharmD         
Sponsors and Collaborators
University of New Mexico
  More Information

No publications provided

Responsible Party: Joe R. Anderson, PharmD, University of New Mexico Health Sciences Center College of Pharmacy
ClinicalTrials.gov Identifier: NCT00690521     History of Changes
Other Study ID Numbers: HRRC 03-477
Study First Received: June 2, 2008
Last Updated: June 3, 2008
Health Authority: United States: Institutional Review Board

Keywords provided by University of New Mexico:
congestive heart failure
diuretics
combination

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Hydrochlorothiazide
Metolazone
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014