Acute Decompensated Heart FailurePhase 4NCT00904488
Oral Metolazone and Intermittent Intravenous Furosemide Versus Continuous Infusion Furosemide in Acute Heart Failure
A Phase 4 study testing Addition of oral Metolazone and Furosemide dose escalation in people with Acute Decompensated Heart Failure, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
The purpose of this prospective, randomized, open-label study is to compare two diuretic strategies in patients with acute decompensated heart failure (ADHF): the addition of an oral thiazide diuretic to intravenous bolus (IVB) loop diuretic will be compared to transition from IVB to continuous infusion (CI) loop… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Decompensated Heart Failure
- What is being tested?
- Addition of oral Metolazone and Furosemide dose escalation
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2008to 14 Nov 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Greater than or equal to 18 years of age
- Hospitalized for acute decompensated heart failure (ADHF) secondary to fluid overload as defined by the presence of at least
- 1 symptom (e.g. dyspnea, orthopnea, paroxysmal nocturnal dyspnea) AND
- 1 sign (e.g. rales on auscultation, > 2+ peripheral or presacral> edema, hepatomegaly, ascites, jugular vein distension > 7 cm, pulmonary vascular congestion on chest radiography)
- Inadequate response to IV diuretics and requiring additional diuresis as determined by primary medical team
- Received less than six doses of IV furosemide OR enrolled within 72 hours of hospital admission
- Anticipated need for intravenous diuretic therapy for at least 48 hours
- Able to provide informed consent
Who cannot join
- Receiving a continuous infusion loop diuretic during current hospital visit
- Substantial diuretic response to pre-randomization diuretic dosing such that higher doses of diuretic would be contraindicated (based on judgement of patient's primary team)
- Planned or ongoing intravenous vasoactive therapy (e.g. inotrope, vasodilator) or mechanical support (e.g. intra-aortic balloon pump, ventricular assist device) for ADHF during this hospitalization
- Planned elective admission for elective placement/revision of a cardiovascular device (e.g. defibrillator, biventricular pacemaker) during this hospitalization or such within the preceding 7 days
- Systolic blood pressure < 90 mmHg
- Serum creatinine > 3 mg/dL at baseline or renal replacement therapy including ultrafiltration
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- Serum potassium < 3.5 mEq/L (3.0 - 3.4 mEq/L allowed if supplemental potassium is being administered)
- Serum magnesium < 1.6 mg/dL (1.4 - 1.5 mg/dL allowed if supplemental magnesium is being administered)
- Acute coronary syndrome or hemodynamically significant arrhythmias causing worsening HF
- Severe, uncorrected primary cardiac valvular disease, acute myocarditis, constrictive pericarditis, hypertrophic obstructive cardiomyopathy, restrictive or constrictive cardiomyopathy, complex congenital heart disease
- Primary pulmonary hypertension with right sided heart failure
- Use of iodinated radiocontrast material in prior 72 hours or planned within the next 48 hours
- Enrollment or planned enrollment in another randomized clinical trial during hospitalization
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Addition of Oral Metolazone to Intermittent Intravenous Furosemide Versus Transition to Continuous Infusion Furosemide in Acute Decompensated Heart Failure Patients Experiencing an Inadequate Response to Therapy
The purpose of this prospective, randomized, open-label study is to compare two diuretic strategies in patients with acute decompensated heart failure (ADHF): the addition of an oral thiazide diuretic to intravenous bolus (IVB) loop diuretic will be compared to transition from IVB to continuous infusion (CI) loop diuretic.
Read the detailed description
Patients hospitalized for ADHF secondary to fluid overload and who are experiencing an inadequate response to IVB furosemide and require additional diuresis will be enrolled. Patients will be randomized to one of two treatment arms: the addition of oral metolazone to continued IVB furosemide versus transition from IVB to CI furosemide. A suggested algorithm for initial dosing and titration of these two diuretic strategies will be provided. Baseline and daily data collection will include various efficacy and safety endpoints including daily net urine output and weight, patient and physician global assessment scale, length of stay, 30-day death or rehospitalization, vital signs, electrolytes, and renal function. Clinically meaningful efficacy and safety endpoints will be compared.
- Conditions
- Acute Decompensated Heart Failure
- Being tested
- Addition of oral Metolazone, Furosemide dose escalation
- Keywords
- Acute Decompensated Heart Failure, Diuretics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Addition of oral MetolazoneDrug
Also called Zaroxolyn
Addition of oral metolazone 5 mg daily to continued current dose of intravenous bolus furosemide
Furosemide dose escalationDrug
Also called Lasix
Furosemide dose escalation via either IV bolus (2-2.5 x current dose) or continuous infusion (2-2.5 x current dose administered over previous 24 hours)
| Study group | Role | What they receive |
|---|---|---|
| Addition of PO Thiazide Diuretic | Active comparator | Addition of oral metolazone 5 mg daily to current intravenous bolus furosemide. All subjects will continue their current dose of intravenous bolus furosemide. Receives: Drug: Addition of oral Metolazone |
| IV furosemide dose escalation | Active comparator | Current IV furosemide dose will be escalated to 2-2.5 x current dose, given as either IV bolus or continuous infusion over 24 hours. Receives: Drug: Furosemide dose escalation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Daily Net Fluid Output on Day 2 (24-48 Hours After Randomization)
Net fluid output = fluid output during 24-48 hours after randomization - fluid intake during 24-48 hours after randomization. A negative value means that daily fluid intake was less than the daily fluid output.
Measured: 24-48 hours
Secondary outcomes (12)
Daily Net Fluid Output on Days 1, 3, and 4
Daily net fluid output = daily fluid output - daily intake. A negative value means that daily fluid intake was less than the daily fluid output.
Measured: 0-24, 48-72, 72-96 hrs
Daily Urine Output (mL Urine Out Per mg Furosemide (IV Equivalent) Received)
Measured: 0-24, 24-48, 48-72, 72-96 hrs
Daily Weight
Measured: Baseline (Dry), Baseline, 0-24, 24-48, 48-72, 72-96 hrs
Patient Global Assessment Scale
Scale range: 1-5 Which of the following best describes your overall health state today?
- = markedly worse
- = worse
- = neither better nor worse
- = better
- = markedly better
Measured: Baseline, 24, 48, 72, 96 hrs
Physician Global Assessment Scale
Scale range: 1-5 Which of the following best describes the patient's overall health state today?
- = markedly worse
- = worse
- = neither better nor worse
- = better
- = markedly better
Measured: Baseline, 24, 48, 72, 96 hours
Need for Additional or Alternative Diuretic (Crossover) or Other Vasoactive Therapy (Study Failure)
Patients will be considered a treatment failure if they require additional diuretic (including crossover to the alternative study arm) or require IV vasoactive drug therapy (e.g. vasodilators including nitroglycerin or inotropes) as deemed appropriate/necessary by their medical team.
Measured: 0-96 hours
Time to Return to Baseline Weight
Measured: 0-96 hours
Length of Hospitalization
Measured: Assessed till hospital discharge, an average of 1 week (longest 29 days)
30-day All-cause Mortality
Measured: 30 days
Rehospitalization at 30 Days
Measured: 30 days
Unscheduled Heart Failure Visits to Emergency Department or Outpatient Clinic
Measured: 30 days
Blood Urea Nitrogen (BUN)
Measured: Baseline, 24, 48, 72, 96 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2009 (estimated)
- Study startOct 2008
- Primary completion28 May 2016
- Study completion14 Nov 2017
Why it stopped: Difficult recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Decompensated Heart FailureStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jo E. Rodgers, PharmD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00904488
- Sponsor's protocol ID
- 08-1292
- Status last verified
- Jan 2018
- First submitted
- 17 May 2009
- Last updated
- 13 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Addition of Oral Metolazone to Intermittent Intravenous Furosemide Versus Transition to Continuous Infusion Furosemide in Acute Decompensated Heart Failure Patients Experiencing an Inadequate Response to Therapy
- ClinicalTrials.gov ID
- NCT00904488
- Acronym / sponsor ID
- 08-1292
- Conditions
- Acute Decompensated Heart Failure
- Keywords
- Acute Decompensated Heart Failure, Diuretics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficult recruitment
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- University of Illinois Chicago, Virginia Commonwealth University
- Study start
- Oct 2008 (actual)
- Primary completion
- 28 May 2016 (actual)
- Study completion
- 14 Nov 2017 (actual)
- First posted
- 19 May 2009 (estimated)
- Results
- Posted 13 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this prospective, randomized, open-label study is to compare two diuretic strategies in patients with acute decompensated heart failure (ADHF): the addition of an oral thiazide diuretic to intravenous bolus (IVB) loop diuretic will be compared to transition from IVB to continuous infusion (CI) loop diuretic.
Detailed description
Patients hospitalized for ADHF secondary to fluid overload and who are experiencing an inadequate response to IVB furosemide and require additional diuresis will be enrolled. Patients will be randomized to one of two treatment arms: the addition of oral metolazone to continued IVB furosemide versus transition from IVB to CI furosemide. A suggested algorithm for initial dosing and titration of these two diuretic strategies will be provided. Baseline and daily data collection will include various efficacy and safety endpoints including daily net urine output and weight, patient and physician global assessment scale, length of stay, 30-day death or rehospitalization, vital signs, electrolytes, and renal function. Clinically meaningful efficacy and safety endpoints will be compared.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Addition of PO Thiazide Diuretic | Active comparator | Drug: Addition of oral MetolazoneAddition of oral metolazone 5 mg daily to current intravenous bolus furosemide. All subjects will continue their current dose of intravenous bolus furosemide. |
| IV furosemide dose escalation | Active comparator | Drug: Furosemide dose escalationCurrent IV furosemide dose will be escalated to 2-2.5 x current dose, given as either IV bolus or continuous infusion over 24 hours. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Greater than or equal to 18 years of age
- Hospitalized for acute decompensated heart failure (ADHF) secondary to fluid overload as defined by the presence of at least
- Inadequate response to IV diuretics and requiring additional diuresis as determined by primary medical team
- Received less than six doses of IV furosemide OR enrolled within 72 hours of hospital admission
- Anticipated need for intravenous diuretic therapy for at least 48 hours
Key exclusion criteria (13 listed)
- Receiving a continuous infusion loop diuretic during current hospital visit
- Substantial diuretic response to pre-randomization diuretic dosing such that higher doses of diuretic would be contraindicated (based on judgement of patient's primary team)
- Planned or ongoing intravenous vasoactive therapy (e.g. inotrope, vasodilator) or mechanical support (e.g. intra-aortic balloon pump, ventricular assist device) for ADHF during this hospitalization
- Planned elective admission for elective placement/revision of a cardiovascular device (e.g. defibrillator, biventricular pacemaker) during this hospitalization or such within the preceding 7 days
- Systolic blood pressure < 90 mmHg
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Addition of oral MetolazoneAlso: ZaroxolynAddition of oral metolazone 5 mg daily to continued current dose of intravenous bolus furosemide | Drug | Addition of PO Thiazide Diuretic |
| Furosemide dose escalationAlso: LasixFurosemide dose escalation via either IV bolus (2-2.5 x current dose) or continuous infusion (2-2.5 x current dose administered over previous 24 hours) | Drug | IV furosemide dose escalation |
Primary outcome
Daily Net Fluid Output on Day 2 (24-48 Hours After Randomization)
Time frame: 24-48 hours
Net fluid output = fluid output during 24-48 hours after randomization - fluid intake during 24-48 hours after randomization. A negative value means that daily fluid intake was less than the daily fluid output.
12 secondary outcomes
Daily Net Fluid Output on Days 1, 3, and 4
Time frame: 0-24, 48-72, 72-96 hrs
Daily Urine Output (mL Urine Out Per mg Furosemide (IV Equivalent) Received)
Time frame: 0-24, 24-48, 48-72, 72-96 hrs
Daily Weight
Time frame: Baseline (Dry), Baseline, 0-24, 24-48, 48-72, 72-96 hrs
Patient Global Assessment Scale
Time frame: Baseline, 24, 48, 72, 96 hrs
Physician Global Assessment Scale
Time frame: Baseline, 24, 48, 72, 96 hours
Need for Additional or Alternative Diuretic (Crossover) or Other Vasoactive Therapy (Study Failure)
Time frame: 0-96 hours
Time to Return to Baseline Weight
Time frame: 0-96 hours
Length of Hospitalization
Time frame: Assessed till hospital discharge, an average of 1 week (longest 29 days)
30-day All-cause Mortality
Time frame: 30 days
Rehospitalization at 30 Days
Time frame: 30 days
Unscheduled Heart Failure Visits to Emergency Department or Outpatient Clinic
Time frame: 30 days
Blood Urea Nitrogen (BUN)
Time frame: Baseline, 24, 48, 72, 96 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jo E. Rodgers, PharmD principal investigator
University of North Carolina, Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Addition of oral Metolazone and Furosemide dose escalation in people with Acute Decompensated Heart Failure, run by University of North Carolina, Chapel Hill at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Daily Net Fluid Output on Day 2 (24-48 Hours After Randomization) (time frame: 24-48 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2018; AzTrials last refreshed its copy on 8 Nov 2026.