Combination Diuretic Therapy for Acute Decompensated Heart Failure

Study Overview
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Brief Summary
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Patients with heart failure are often admitted to the hospital because they have accumulated excessive amounts of fluid, they become short of breath and congested with fluid. Removing the excess fluid is necessary to improve the patients symptoms and reduce the risk of being re-admitted to the hospital. Diuretics (water pills) are often given through an IV to accelerate the fluid removal. Furosemide is commonly used for fluid removal, however some patients do not respond well to the medication. There are other diuretics available that can work in conjunction with furosemide and increase the rate of fluid removal. The other water pills have slightly different mechanisms of action in the body compared to furosemide and when combined they may increase fluid removal. The investigators hypothesize that adding chlorothiazide to furosemide will result in quicker and more effective fluid removal in heart failure patients.

Detailed Description
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The investigators will randomly assign patients to receive either furosemide alone or furosemide in combination with chlorothiazide when they are admitted to the hospital with acute heart failure and excessive volume. All patients will be monitored for rate of fluid removal, improvement in symptoms, and side-effects of the medications.

Official Title
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Efficacy and Tolerability of Combination Intravenous Diuretic Therapy Versus Intravenous Loop Diuretic Therapy Alone for the Treatment of Acute Decompensated Heart Failure

Conditions
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Acute Decompensated Heart Failure

Intervention / Treatment
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* Drug: Furosemide plus Chlorothiazide
* Drug: Furosemide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Acute Decompensated Heart Failure - by at least 1 symptom (dyspnea, exercise intolerance, weight gain, edema) and at least 1 sign (chest x-ray (CXR), elevated brain natriuretic peptide (BNP), rales, elevated jugular venous pressure (JVP)). History of Congestion Heart Failure (CHF) with chronic loop diuretic use for at least the past 4 weeks Echocardiogram in the past 12 months (to document Ejection fraction (EF)) Exclusion Criteria: Chronic Kidney Disease (CKD) or Acute Kidney Injury (AKI) - Cr >2.5 mg/dL Ventricular assist device Cardiogenic shock Need for mechanical or vasopressor support on admission Significant co-morbidities: Chronic Obstructive Pulmonary Disease, pneumonia, pulmonary embolism History of pulmonary hypertension (PAH) (World Health Organization (WHO) group I primary PAH) Acute Ischemia / post-intervention (Coronary Artery Bypass Graft, Percutaneous Coronary Interventions) in the past 90 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination Diuretic Therapy<br>Patients will receive lasix infusion starting at 5mg/hr along with a bolus dose of chlorothiazide 250mg at the initiation of the protocol. The lasix infusion can be titrated to 10mg after 12hrs based on volume of diuresis. This arm will also receive 250mg bolus doses of chlorothiazide every 12hrs for the duration of the study. | Drug: Furosemide plus Chlorothiazide<br>* Patients will receive lasix infusion starting at 5mg/hr along with a bolus dose of chlorothiazide 250mg at the initiation of the protocol. The lasix infusion can be titrated to 10mg after 12hrs based on volume of diuresis. This arm will also receive 250mg bolus doses of chlorothiazide every 12hrs for the duration of the study. Intravenous (IV) lasix infusion at 5mg/hr plus IV boluses of diuril every 12 hrs.<br>* Other names: Lasix plus Diuril;Drug: Furosemide<br>* Patients will receive furosemide infusion at 5mg/hr along with an initial bolus dose of furosemide equal to twice their home oral dose. The furosemide infusion can be increased to 10mg/hr after 12hrs based on urine output. This arm will receive bolus doses of furosemide every 12hrs equal to twice their home oral dose until completion of the protocol.<br>* Other names: Lasix;|
| Active Comparator: Monotherapy Diuretic<br>Patients will receive furosemide infusion at 5mg/hr along with an initial bolus dose of furosemide equal to twice their home oral dose. The furosemide infusion can be increased to 10mg/hr after 12hrs based on urine output. This arm will receive bolus doses of furosemide every 12hrs equal to twice their home oral dose until completion of the protocol. | Drug: Furosemide<br>* Patients will receive furosemide infusion at 5mg/hr along with an initial bolus dose of furosemide equal to twice their home oral dose. The furosemide infusion can be increased to 10mg/hr after 12hrs based on urine output. This arm will receive bolus doses of furosemide every 12hrs equal to twice their home oral dose until completion of the protocol.<br>* Other names: Lasix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volume of Diuresis | Total volume of urine output will be collected during the first 72 hours of admission. | During Index Hospitalization at 72 hours | 
| Change in Serum Creatinine from Baseline | Change in serum creatinine from baseline after 72 hours of diuresis | During Index Admission up to 120 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypokalemia |  | From date of index hospitalization until 72 hours after diuresis | 
| Electrolyte Disturbances | Magnesium, Phosphorous | From date of index hospitalization until 72 hours after diuresis | 
| Total Weight Loss |  | From date of index hospitalization until 72 hours after diuresis | 
| Relief of Symptoms | Using the five-point Likert scale for dyspnea which ranges from 1-5 where the lower the score the better the outcome | From date of index hospitalization until 72 hours after diuresis | 
| Length of Stay |  | From date of index hospitalization until date of discharge from hospital, assessed up to 1 week | 
| Potassium Replacement Requirements |  | From date of index hospitalization until date of discharge from hospital, assessed up to 1 week | 
| Adverse Events | Hypotension, dizziness, syncope, acute renal failure, arrhythmia | From date of index hospitalization until date of discharge from hospital, assessed up to 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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heart failure, acute, diuretic, management, renal function, chlorothiazide, furosemide