NCT03574857

Brief Summary

The primary objective of the study is to compare efficacy of metolazone and chlorothiazide as add-on therapy in patients refractory to loop diuretics with heart failure with a reduced ejection fraction (HFrEF). This will be a single-center randomized pilot study.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5

participants targeted

Target at below P25 for phase_4 heart-failure

Timeline
Completed

Started Jun 2018

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 16, 2018

Completed
2 months until next milestone

Study Start

First participant enrolled

June 1, 2018

Completed
1 month until next milestone

First Posted

Study publicly available on registry

July 2, 2018

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2021

Completed
Last Updated

February 16, 2021

Status Verified

February 1, 2021

Enrollment Period

2.6 years

First QC Date

April 16, 2018

Last Update Submit

February 10, 2021

Conditions

Heart FailureHeart Failure With Reduced Ejection FractionHeart Failure AcuteCardiovascular Diseases

Keywords

Loop diureticsHeart failureDiuretic resistanceThiazide diuretics

Outcome Measures

Primary Outcomes (1)

  • Net urine output at 24 hours

    Milliliters of urine output minus the oral plus intravenous intake

    24 hours

Secondary Outcomes (4)

  • Net urine output at 48 hours

    48 hours

  • Net fluid balance over 12 hours

    24 hours

  • Net fluid balance over 24 hours

    48 hours

  • Weight change

    48 hours

Other Outcomes (5)

  • Electrolyte disturbances

    48 hours

  • Worsening renal function

    48 hours

  • Hospital length of stay

    Assessed until hospital discharge, an average of 7 days

  • +2 more other outcomes

Study Arms (2)

Metolazone

ACTIVE COMPARATOR

Metolazone 5 mg by mouth once daily for 2 days

Drug: Metolazone Oral Tablet

Chlorothiazide

ACTIVE COMPARATOR

Chlorothiazide 500 mg IV once daily for 2 days

Drug: Chlorothiazide Injection

Interventions

Metolazone Oral TabletDRUG

Day 1: Metolazone 5 mg PO Day 2: Metolazone 5 mg PO

Also known as: Zaroxolyn
Metolazone
Chlorothiazide InjectionDRUG

Day 1: Chlorothiazide 500 mg IV Day 2: Chlorothiazide 500 mg IV

Also known as: Diuril
Chlorothiazide

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age \> 18 years old
  • Admitted for acute decompensated HF with left ventricular ejection fraction (LVEF) \<40%
  • Refractory fluid overload:
  • Unresponsive (\<500 mL net negative over previous 24 hours) AND ineffective diuresis (determined by HF team) to moderate intensity push or low intensity continuous infusion loop diuretic (80 mg IV furosemide or equivalent bumetanide dose of 4 mg)
  • English or Spanish-speaking subjects
  • Willing and able to comply with study procedures

You may not qualify if:

  • Baseline thiazide use prior to admission or prior to study enrollment
  • Renal replacement therapies (RRT) or glomerular filtration rate (GFR) \<30 mL/min at the time of enrollment
  • Pregnant women
  • Cognitive impairment
  • Prisoners
  • Left ventricular assist devices (LVAD) or temporary mechanical circulatory support devices
  • History of cardiac transplant
  • Reported allergy to thiazides
  • No enteral access or unable to take medications enterally
  • Palliative diuretics
  • Systolic blood pressure (SBP) \<90 mm Hg prior to randomization
  • Patients receiving concomitant lithium therapy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Heart FailureCardiovascular Diseases

Interventions

MetolazoneChlorothiazide

Condition Hierarchy (Ancestors)

Heart Diseases

Intervention Hierarchy (Ancestors)

SulfonamidesAmidesOrganic ChemicalsSulfonesSulfur CompoundsQuinazolinonesQuinazolinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsBenzothiadiazinesThiazides

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principle Investigator

Study Record Dates

First Submitted

April 16, 2018

First Posted

July 2, 2018

Study Start

June 1, 2018

Primary Completion

January 1, 2021

Study Completion

January 1, 2021

Last Updated

February 16, 2021

Record last verified: 2021-02

Locations

US(1)