Acute Decompensated Heart FailurePhase 3MELT-HFNCT02620384
Metolazone As Early Add On Therapy For Acute Decompensated Heart Failure (MELT-HF)--A Single Center Pilot Study.
A Phase 3 study testing Experimental: Metolazone in people with Acute Decompensated Heart Failure, run by Aultman Health Foundation at 1 site in United States.
Trial 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 single center double blinded randomized placebo- controlled pilot study of the addition of 5 mg of metolazone per day for 2 days compared to… 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?
- Experimental: Metolazone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 147 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2015to 29 Dec 2017
- Phase
- Phase 3
- 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
- Age 18 years or older
- Current hospitalization for chronic congestive heart failure with admission up to 48 hours prior to inclusion.
- Chronic heart failure will be defined as requiring treatment for a minimum of 30 days prior to current admission, NYHA Class III or IV at the time of hospitalization, and left ventricular ejection fraction less than 40% within one year or evidence of heart failure with preserved ejection fraction and evidence of diastolic dysfunction on echocardiogram.
- Admitted with clinical decompensated heart failure based on history, physical exam, and parameters indicating extracellular volume expansion such as including JVP ≥ 8 cm of water and 1+ or greater peripheral edema
- Is able to be dosed with study medication within six (6) hours of first dose of IV diuretics
Who cannot join
- Baseline severe hypotension (Mean arterial pressure < 55 mm Hg)
- Creatinine clearance less than 20 ml/min or creatinine greater than 2.5 mg/dl.
- Serum sodium less than 128 meq/L.
- Serum Potassium < 3.0 meq/L.
- Known adverse reaction to metolazone
- Inability to take oral medications
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- Severe Aortic Stenosis (AVA < 0.8cm2)
- History of Hypertrophic obstructive cardiomyopathy
- Metastatic Carcinoma per history
- Severe COPD, FEV < 1L
- Severe dyspnea requiring prolonged CPAP,BIPAP or intubation
Trial locations and contacts
1 site in 1 country.
About this study
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 single center 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.
Read the detailed description
Heart failure is a major source of morbidity, mortality and growing public health cost. In US, the number of congestive heart failure patients is more than 4 million with more than 550,000 new annually reported cases. The annual cost of heart failure management exceeds 35 billion dollars per year.The heart failure readmissions and average length of hospital stay cost approximately $11,000 per patient.
Loop diuretics are used alone in the majority of cases to promote diuresis. An association of increased creatinine and increased risk of renal dysfunction, the cardiorenal syndrome, in the face of high dose loop diuretics has raised questions regarding the safety and toxicity of high dose loop diuretics. While the dose of diuretics is ubiquitous, little data exists to guide their use and many clinicians are uncertain as to when and how to initiate and limit therapy.
Prospective randomized data on large number of decompensated heart failure patients receiving metolazone in addition to standard therapy is scarce and needs further definitive evaluation in terms of clinical outcomes and safety. In many cases, a "stepped approach" with oral loop diuretics advancing to intravenous and finally combination high dose diuretics is employed.
Primary endpoint: Total urinary output and negative fluid balance in millilitres (ml) at 48 hours following first dose of intravenous diuretic.
Secondary endpoints:
- Change in weight from admission to day 2.
- Degree of improvement in dyspnea at 6,12, 24,36, and 48 hours assessed with Modified Borg Scale (1-10)
- All cause mortality at 30 days.
This is a single center study of at least 200 patients who are admitted to Aultman Hospital with clinical decompensated congestive heart failure ( NYHA III-IV). It is a 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. We will compare a strategy of early institution of metolazone with standard of care in patients admitted with decompensated heart failure and volume overload. 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. Two additional doses of metolazone within 6 and 24 hours of administration of standard intravenous diuretics will be given to the treatment arm. Patients and physicians will be blinded to the administered drug (metolazone vs placebo).Drug will be distributed by pharmacy when a patient is consented and enrolled in the trial. Specific guidance/recommendations regarding diuretic therapy will be provided (documented in detail below) but will be at the discretion of the treating physician. We will collect data on demographics, co-morbidities, clinical presentations and outcomes with metolazone administration with patient follow up at one week (+3) and 30 (±7) days post discharge.
- Conditions
- Acute Decompensated Heart Failure
- Being tested
- Experimental: Placebo, Experimental: Metolazone
- Keywords
- Metolazone, Heart Failure
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Experimental: PlaceboDrug
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 admininstration of first dose of intravenous diuretic. The second placebo dose is given at 24-hours after the first dose.
Experimental: MetolazoneDrug
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 admininstration of first dose of intravenous diuretic The second dose of metolazone is given 24-hours after the first dose.
| Study group | Role | What they receive |
|---|---|---|
| Experimental: Placebo | Placebo comparator | This group will receive all standard heart failure therapy and placebo pill. Receives: Drug: Experimental: Placebo |
| Experimental: Metolazone | Active comparator | This group will receive all standard heart failure therapy with addition of metolazone. Receives: Drug: Experimental: Metolazone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Urinary Output at 48 Hours
Total urinary output in milliliters (ml) at 48 hours. Measurement timing began with administration of first dose of investigational product, ended 48 hours later.
Measured: 48 hours
Fluid Balance at 48 Hours
Difference in value between input and output in milliliters (ml) at 48 hours. Measurement timing began with administration of first dose of investigational product, ended 48 hours later. Fluid balance = Fluid in minus Fluid out.
Measured: 48 hours
Secondary outcomes (5)
Change in Weight First 48 Hours
Change in weight from the date/time of study enrollment (baseline) and 48 hours.
Measured: 48 hours
Degree of Improvement in Dyspnea at 6, 12, 24, 36 and 48 Hours.
Dyspnea assessed at 6, 12, 24, 36 and 48 hours with Modified Borg Scale (1-10). Range is from 1 (very slight) to 10 (maximal) dyspnea.
Measured: 6, 12, 24, 36 and 48 hours.
Total Dose Diuretics First 48 Hours
Total dosage loop diuretic in first 48 hours using conversion tool to calculate intravenous Lasix equivalence
Measured: 48 hours
Number of Participants With Inotrope Administration During First 48 Hours
Number of Participants with Inotrope administration during first 48 hours following study enrollment.
Measured: 48 hours
All Cause Mortality at 30 Days
All Cause Mortality at 30 Days
Measured: 30 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2015 (estimated)
- Study start1 Oct 2015
- Primary completion29 Nov 2017
- Study completion29 Dec 2017
Why it stopped: Limited resources available to met accrual goal.
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.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 147 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aultman Health Foundation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Muhammad Chaudhry, MD, Principal investigator, Aultman Health Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02620384
- Sponsor's protocol ID
- 2015.03.26.F2
- Acronym
- MELT-HF
- Status last verified
- Jan 2019
- First submitted
- 1 Dec 2015
- Last updated
- 15 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metolazone As Early Add On Therapy For Acute Decompensated Heart Failure (MELT-HF)--A Single Center Pilot Study.
- ClinicalTrials.gov ID
- NCT02620384
- Acronym / sponsor ID
- MELT-HF / 2015.03.26.F2
- Conditions
- Acute Decompensated Heart Failure
- Keywords
- Metolazone, Heart Failure
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Limited resources available to met accrual goal.
- Enrolment
- 147 participants (actual)
- Lead sponsor
- Aultman Health FoundationUniversity, hospital or other
- Study start
- 1 Oct 2015 (actual)
- Primary completion
- 29 Nov 2017 (actual)
- Study completion
- 29 Dec 2017 (actual)
- First posted
- 3 Dec 2015 (estimated)
- Results
- Posted 15 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 single center 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
Heart failure is a major source of morbidity, mortality and growing public health cost. In US, the number of congestive heart failure patients is more than 4 million with more than 550,000 new annually reported cases. The annual cost of heart failure management exceeds 35 billion dollars per year.The heart failure readmissions and average length of hospital stay cost approximately $11,000 per patient.
Loop diuretics are used alone in the majority of cases to promote diuresis. An association of increased creatinine and increased risk of renal dysfunction, the cardiorenal syndrome, in the face of high dose loop diuretics has raised questions regarding the safety and toxicity of high dose loop diuretics. While the dose of diuretics is ubiquitous, little data exists to guide their use and many clinicians are uncertain as to when and how to initiate and limit therapy.
Prospective randomized data on large number of decompensated heart failure patients receiving metolazone in addition to standard therapy is scarce and needs further definitive evaluation in terms of clinical outcomes and safety. In many cases, a "stepped approach" with oral loop diuretics advancing to intravenous and finally combination high dose diuretics is employed.
Primary endpoint: Total urinary output and negative fluid balance in millilitres (ml) at 48 hours following first dose of intravenous diuretic.
Secondary endpoints:
- Change in weight from admission to day 2.
- Degree of improvement in dyspnea at 6,12, 24,36, and 48 hours assessed with Modified Borg Scale (1-10)
- All cause mortality at 30 days.
This is a single center study of at least 200 patients who are admitted to Aultman Hospital with clinical decompensated congestive heart failure ( NYHA III-IV). It is a 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. We will compare a strategy of early institution of metolazone with standard of care in patients admitted with decompensated heart failure and volume overload. 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. Two additional doses of metolazone within 6 and 24 hours of administration of standard intravenous diuretics will be given to the treatment arm. Patients and physicians will be blinded to the administered drug (metolazone vs placebo).Drug will be distributed by pharmacy when a patient is consented and enrolled in the trial. Specific guidance/recommendations regarding diuretic therapy will be provided (documented in detail below) but will be at the discretion of the treating physician. We will collect data on demographics, co-morbidities, clinical presentations and outcomes with metolazone administration with patient follow up at one week (+3) and 30 (±7) days post discharge.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental: Placebo | Placebo comparator | Drug: Experimental: PlaceboThis group will receive all standard heart failure therapy and placebo pill. |
| Experimental: Metolazone | Active comparator | Drug: Experimental: MetolazoneThis group will receive all standard heart failure therapy with addition of metolazone. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age 18 years or older
- Current hospitalization for chronic congestive heart failure with admission up to 48 hours prior to inclusion.
- Chronic heart failure will be defined as requiring treatment for a minimum of 30 days prior to current admission, NYHA Class III or IV at the time of hospitalization, and left ventricular ejection fraction less than 40% within one year or evidence of heart failure with preserved ejection fraction and evidence of diastolic dysfunction on echocardiogram.
- Admitted with clinical decompensated heart failure based on history, physical exam, and parameters indicating extracellular volume expansion such as including JVP ≥ 8 cm of water and 1+ or greater peripheral edema
- Is able to be dosed with study medication within six (6) hours of first dose of IV diuretics
Key exclusion criteria (11 listed)
- Baseline severe hypotension (Mean arterial pressure < 55 mm Hg)
- Creatinine clearance less than 20 ml/min or creatinine greater than 2.5 mg/dl.
- Serum sodium less than 128 meq/L.
- Serum Potassium < 3.0 meq/L.
- Known adverse reaction to metolazone
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 |
|---|---|---|
| Experimental: PlaceboAll 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 admininstration of first dose of intravenous diuretic. The second placebo dose is given at 24-hours after the first dose. | Drug | Experimental: Placebo |
| Experimental: MetolazoneAll 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 admininstration of first dose of intravenous diuretic The second dose of metolazone is given 24-hours after the first dose. | Drug | Experimental: Metolazone |
Primary outcome
Total Urinary Output at 48 Hours
Time frame: 48 hours
Total urinary output in milliliters (ml) at 48 hours. Measurement timing began with administration of first dose of investigational product, ended 48 hours later.
Fluid Balance at 48 Hours
Time frame: 48 hours
Difference in value between input and output in milliliters (ml) at 48 hours. Measurement timing began with administration of first dose of investigational product, ended 48 hours later. Fluid balance = Fluid in minus Fluid out.
5 secondary outcomes
Change in Weight First 48 Hours
Time frame: 48 hours
Degree of Improvement in Dyspnea at 6, 12, 24, 36 and 48 Hours.
Time frame: 6, 12, 24, 36 and 48 hours.
Total Dose Diuretics First 48 Hours
Time frame: 48 hours
Number of Participants With Inotrope Administration During First 48 Hours
Time frame: 48 hours
All Cause Mortality at 30 Days
Time frame: 30 Days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2019.
- 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.
Muhammad Chaudhry, MD principal investigator
Aultman Health Foundation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Experimental: Metolazone in people with Acute Decompensated Heart Failure, run by Aultman Health Foundation 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 5 inclusion and 11 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 15 Feb 2019. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 15 Feb 2019). 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?
Total Urinary Output at 48 Hours (time frame: 48 hours). The study lists 2 primary outcomes in all. 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 15 Feb 2019.