Metolazone As Early Add On Therapy For Acute Decompensated Heart Failure

Study Overview
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Brief Summary
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The primary objective of the study is to determine efficacy of metolazone as synergistic therapy with Lasix in patients with acute decompensated heart failure. This will be a multicenter double blinded randomized placebo- controlled pilot study of the addition of 5 mg of metolazone per day for 2 days compared to placebo in patients admitted with acute decompensated heart failure.

Detailed Description
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AS DESCRIBED BY THE PRINCIPAL INVESTIGATOR (DR. HEYWOOD): The primary objective of the study is to determine efficacy of metolazone as synergistic therapy with Lasix in patients with acute decompensated heart failure. This will be a multicenter double blinded randomized placebo- controlled pilot study of the addition of 5 mg of metolazone per day for 2 days compared to placebo in patients admitted with acute decompensated heart failure.

Official Title
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Metolazone As Early Add On Therapy For Acute Decompensated Heart Failure (MELT-HF): A Multicenter, Randomized Controlled Trial.

Conditions
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Acute Decompensated Heart Failure

Intervention / Treatment
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* Drug: Placebo
* Drug: Metolazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is 18 years of age at time of enrollment. Admitted with acute decompensated heart failure based on history, physical exam, and laboratory parameters, must include both: At least 1 symptom of either dyspnea, orthopnea, or edema. At least 1 sign of rales on auscultation, peripheral edema, ascites, or pulmonary vascular congestion on chest radiography. Be willing to comply with protocol-specified instructions Able to understand and grant informed consent. Exclusion Criteria: Inability to give informed consent. Systolic BP < 90 mmHg Creatinine clearance less than 20ml/min or creatinine greater than 2.5mg/dl. Serum Sodium less than 128meq/L, potassium levels less than 3.5meq/L Known adverse reaction to metolazone Inability to take oral medications Severe Aortic Stenosis (AVA < 0.8cm³) History of Hypertrophic Obstructive Cardiomyopathy. Metastatic Carcinoma Severe Chronic Obstructive Pulmonary Disease (COPD), FEV < 1L Severe dyspnea requiring prolonged CPAP or intubation Moderate/Severe Dementia

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: SOC heart failure therapy and placebo pill (Arm A)<br>This group will receive all standard heart failure therapy and placebo pill. | Drug: Placebo<br>* All patients will receive standard heart failure therapy, including but not restricted to diuretics, digoxin, angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, beta blockers, aldosterone antagonists, hydralazine, and/or nitrates, at the discretion of the treating physician. After informed consent is obtained, patients will be randomized 1:1 to the treatment arm or placebo arm. The first placebo dose is given within six hours of administration of first dose of intravenous diuretic. The second placebo dose is given at 24-hours after the first dose.<br>* Other names: NA-placebo;|
| Active Comparator: SOC heart failure therapy with addition of metolazone (Arm B)<br>This group will receive all standard heart failure therapy with addition of metolazone. | Drug: Metolazone<br>* All patients will receive standard heart failure therapy, including but not restricted to diuretics, digoxin, angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, beta blockers, aldosterone antagonists, hydralazine, and/or nitrates, at the discretion of the treating physician. After informed consent is obtained, patients will be randomized 1:1 to the treatment arm or placebo arm. The first dose of metolazone is given within six hours of administration of first dose of intravenous diuretic The second dose of metolazone is given 24-hours after the first dose.<br>* Other names: NA-Metolazone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total urinary output and negative fluid balance | Total urinary output and negative fluid balance in milliliters (ml) at 48 hours following administration of first dose of intravenous diuretic. | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in weight | Change in weight from admission to day 2 | Day 2 | 
| Degree of improvement in dyspnea | Dyspnea assessed at 6, 12, 24, 36, and 48 hours with Modified Borg Scale (1-10) | 6, 12, 24, 36, and 48 hours | 
| All cause mortality | All-cause mortality at 30 days | 30 days |