Metolazone As Early Add On Therapy For Acute Decompensated Heart Failure (MELT-HF)

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Acute Decompensated Heart Failure
• Intervention / Treatment: Drug: Placebo; Drug: Metolazone

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Scripps Green Torrey Pines

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. At least 1 symptom of either dyspnea, orthopnea, or edema.
  2. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: SOC heart failure therapy and placebo pill (Arm A); This group will receive all standard heart failure therapy and placebo pill.	Drug: Placebo; 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.; Other Names: NA-placebo
Active Comparator: SOC heart failure therapy with addition of metolazone (Arm B); This group will receive all standard heart failure therapy with addition of metolazone.	Drug: Metolazone; 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.; Other Names: NA-Metolazone

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Scripps Health
• Investigators: Principal Investigator: James T Heywood, MD, Scripps Health

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: November 21, 2022
• First Submitted That Met QC Criteria: November 21, 2022
• First Posted (Actual): December 1, 2022

Study Record Updates

• Last Update Posted (Actual): December 1, 2022
• Last Update Submitted That Met QC Criteria: November 21, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Chloride Symporter Inhibitors; Metolazone
• Other Study ID Numbers: IRB-14-6311

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No