Congestive Heart Failure
Conditions
Keywords
congestive heart failure, diuretics, combination
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
Interventions
DRUGTreatment 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.
DRUGTreatment 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.
Sponsors
University of New Mexico
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 98 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Participants With Change in Urinary Output | First Intervention (4 days), Washout (7 days), and Second Intervention (4 days) |
Countries
United States
Participant flow
Recruitment details
8 patients enrolled and received drug treatment.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 A Randomized, double-blind, crossover study designed to compare the efficacy of furosemide in combination with hydrochlorothiazide or metolazone in congestive heart failure patients.
First Intervention with Furosemide and Hydrochlorothiazide (4 days), Washout (7 days), and Second Intervention with Furosemide + Metolazone(4 days). | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Arm 1 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Race/Ethnicity, Customized Hispanic | 3 participants |
| Race/Ethnicity, Customized Other | 5 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 |
Outcome results
Primary
Participants With Change in Urinary Output
Time frame: First Intervention (4 days), Washout (7 days), and Second Intervention (4 days)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm1- Furosemide and Hydrochlorothiazide Then Furosemide + Metolazone | Participants With Change in Urinary Output | First Intervention (4 days) | 4 participants |
| Arm1- Furosemide and Hydrochlorothiazide Then Furosemide + Metolazone | Participants With Change in Urinary Output | Washout (7 days) | 4 participants |
| Arm1- Furosemide and Hydrochlorothiazide Then Furosemide + Metolazone | Participants With Change in Urinary Output | Second Intervention (4 days) | 4 participants |
| Arm2-Furosemide and Metolazone Then Furosemide and Hydrochlorothiazide | Participants With Change in Urinary Output | First Intervention (4 days) | 4 participants |
| Arm2-Furosemide and Metolazone Then Furosemide and Hydrochlorothiazide | Participants With Change in Urinary Output | Washout (7 days) | 4 participants |
| Arm2-Furosemide and Metolazone Then Furosemide and Hydrochlorothiazide | Participants With Change in Urinary Output | Second Intervention (4 days) | 4 participants |