Metolazone As Early Add On Therapy For Acute Decompensated Heart Failure

NCT05633758 | Withdrawn Phase 2

• 1 other identifier: IRB-14-6311
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Decompensated Heart Failure

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Change in weight

  Day 2

• Degree of improvement in dyspnea

  6, 12, 24, 36, and 48 hours

• All cause mortality

  30 days

Study Arms (2)

SOC heart failure therapy and placebo pill (Arm A)

PLACEBO COMPARATOR

This group will receive all standard heart failure therapy and placebo pill.

Drug: Placebo

SOC heart failure therapy with addition of metolazone (Arm B)

ACTIVE COMPARATOR

This group will receive all standard heart failure therapy with addition of metolazone.

Drug: Metolazone

Interventions

Placebo DRUG

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.

Also known as: NA-placebo

SOC heart failure therapy and placebo pill (Arm A)

Metolazone DRUG

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.

Also known as: NA-Metolazone

SOC heart failure therapy with addition of metolazone (Arm B)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Scripps Health: lead

Study Sites (1)

Scripps Green Torrey Pines

La Jolla, California, 92037, United States

Location

MeSH Terms

Interventions

Metolazone

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Quinazolinones; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• James T Heywood, MD

  Scripps Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2022
• First Posted: December 1, 2022
• Study Start: March 1, 2014
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: December 1, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)