Fluid OverloadPhase 4NCT03746002
Diuretic Effect of Metolazone Pre-dosing Versus Concurrent Dosing
A Phase 4 study testing Metolazone 60 minutes prior to furosemide and Metolazone concurrently with furosemide in people with Fluid Overload and Heart Failure Acute, run by University of Maryland, Baltimore at 1 site in United States.
Trial summary
The purpose of this study is to examine whether administering metolazone 60 minutes prior to furosemide increases urine output compared with administering metolazone and furosemide concomitantly. Participants will have equal chance of being assigned to each group. Read more about this study
- Who is it for?
- Ages 18 to 89 years
- Conditions the study is for
- Fluid Overload, Heart Failure Acute
- What is being tested?
- Metolazone 60 minutes prior to furosemide and Metolazone concurrently with furosemide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2019to 10 Jan 2020
- 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 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Admission within 48 hours for acute decompensated heart failure with at least one symptom and one sign of volume overload
- Receipt of loop diuretic prior to admission
- Plan to administer furosemide 120 - 160 mg IV bolus twice daily over the next 24 hours with additional diuresis deemed necessary
- If patient is concurrently administered intravenous vasodilator or inotrope, the dose of vasodilator or inotrope must be stable for 6 hours prior to enrollment with a plan to continue the same dose for the 24 hour duration of this study
Who cannot join
- Metolazone prescribed prior to admission
- Receipt of continuous intravenous infusion of furosemide
- Cirrhosis or end stage renal disease
- Non-English speaking patients
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Maryland Medical Center
Baltimore, Maryland, 21201
About this study
Official title: Diuretic Effect of Metolazone Pre-dosing Versus Concurrent Dosing With Furosemide: a Pilot Study
The purpose of this study is to examine whether administering metolazone 60 minutes prior to furosemide increases urine output compared with administering metolazone and furosemide concomitantly. Participants will have equal chance of being assigned to each group.
Read the detailed description
Diuretic resistance is common among patients with acute decompensated heart failure, and one strategy for overcoming this phenomenon is sequential nephron blockade with loop plus thiazide-type diuretics. Metolazone is an oral thiazide-type diuretic commonly used for this purpose. Due to its delayed absorption, some clinicians suggest that metolazone be given 30-60 minutes prior to the loop diuretic. However, the efficacy and safety of such a strategy has not been investigated despite its added complexity. The purpose of this study is to investigate whether pre-dosing with metolazone confers a difference in efficacy and safety compared to administering it at the same time as furosemide.
- Conditions
- Fluid Overload, Heart Failure Acute
- Being tested
- Metolazone 60 minutes prior to furosemide, Metolazone concurrently with furosemide
- Keywords
- diuretic, metolazone, furosemide
- Medical subject headings
- Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metolazone 60 minutes prior to furosemideDrug
Also called Zaroxolyn
All patients will receive furosemide background therapy (furosemide 120 - 160 mg IV bolus dosed twice within a twenty four hour period. Patients will be randomized 1:1 to either metolazone 5 mg tablet dosed 60 minutes prior to first dose of furosemide or metolazone dosed concurrently (within ten minute time frame) with the first dose of furosemide.
Metolazone concurrently with furosemideDrug
Also called Zaroxolyn
All patients will receive furosemide background therapy (furosemide 120 - 160 mg IV bolus dosed twice within a twenty four hour period. Patients will be randomized 1:1 to either metolazone 5 mg tablet dosed 60 minutes prior to first dose of furosemide or metolazone dosed concurrently (within ten minute time frame) with the first dose of furosemide.
| Study group | Role | What they receive |
|---|---|---|
| Metolazone Pre-dosing | Active comparator | Metolazone 5 mg by mouth administered 60 minutes prior to furosemide background therapy (120 - 160 mg intravenous bolus, followed by furosemide 120 - 160 mg intravenous bolus 12 - 24 hours after) Receives: Drug: Metolazone 60 minutes prior to furosemide |
| Metolazone Concurrent Dosing | Active comparator | Metolazone 5 mg by mouth administered at the same time as furosemide background therapy (120 - 160 mg intravenous bolus, followed by furosemide 120 - 160 mg intravenous bolus 12 - 24 hours after) Receives: Drug: Metolazone concurrently with furosemide |
What is being measured
The primary outcome is the main question the study is designed to answer.
24-Hour Urine Output
Total measured urine output in milliliters produced after metolazone dose is given
Measured: 24 hours
Secondary outcomes (6)
Change in Total Body Weight
Change in total body weight from baseline value measured prior to metolazone dose to value collected after metolazone dose
Measured: Baseline and at 12 to 23 hours after metolazone dose
Change in Serum Creatinine
Change in serum creatinine from baseline value collected prior to metolazone dose to value collected after metolazone dose
Measured: Baseline and at 12 to 23 hours after metolazone dose
Acute Kidney Injury
Portion of patients with increase in serum creatinine by ≥ 0.3 mg/dL or ≥ 50% from baseline
Measured: Baseline and at 12 to 23 hours after metolazone dose
Hypokalemia
Proportion of patients with potassium level less than 4.0 mEq/L measured after metolazone dose is given
Measured: Baseline and at 12 to 23 hours after metolazone dose
Hypomagnesemia
Proportion of patients with magnesium level less than 2.0 mg/dL measured after metolazone dose is given
Measured: Baseline and at 12 to 23 hours after metolazone dose
Hyponatremia
Proportion of patients with serum sodium level less than 135 mg/dL measured after metolazone dose is given
Measured: Baseline and at 12 to 23 hours after metolazone dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2018
- Study start1 Jan 2019
- Primary completion10 Jan 2020
- Study completion10 Jan 2020
Why it stopped: Insufficient rate of patient enrollment/accrual.
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.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Fluid OverloadStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe 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
- Model description
- Prospective, randomized, open-label, active control pilot study
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brent Reed, University of Maryland, Baltimore
- Investigators
- Brent Reed, PharmD, Principal investigator, University of Maryland, College Park
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03746002
- Sponsor's protocol ID
- HP-00082982
- Status last verified
- Sep 2021
- First submitted
- 15 Nov 2018
- Last updated
- 22 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ellison DH, Felker GM. Diuretic Treatment in Heart Failure. N Engl J Med. 2017 Nov 16;377(20):1964-1975. doi: 10.1056/NEJMra1703100. No abstract available.
PubMed 29141174Jentzer JC, DeWald TA, Hernandez AF. Combination of loop diuretics with thiazide-type diuretics in heart failure. J Am Coll Cardiol. 2010 Nov 2;56(19):1527-34. doi: 10.1016/j.jacc.2010.06.034.
PubMed 21029871Grosskopf I, Rabinovitz M, Rosenfeld JB. Combination of furosemide and metolazone in the treatment of severe congestive heart failure. Isr J Med Sci. 1986 Nov;22(11):787-90.
PubMed 3793436Ellison DH. The physiologic basis of diuretic synergism: its role in treating diuretic resistance. Ann Intern Med. 1991 May 15;114(10):886-94. doi: 10.7326/0003-4819-114-10-886.
PubMed 2014951
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diuretic Effect of Metolazone Pre-dosing Versus Concurrent Dosing With Furosemide: a Pilot Study
- ClinicalTrials.gov ID
- NCT03746002
- Acronym / sponsor ID
- HP-00082982
- Conditions
- Fluid Overload, Heart Failure Acute
- Keywords
- diuretic, metolazone, furosemide
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient rate of patient enrollment/accrual.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 10 Jan 2020 (actual)
- Study completion
- 10 Jan 2020 (actual)
- First posted
- 19 Nov 2018 (actual)
- Results
- Posted 22 Oct 2021
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 study is to examine whether administering metolazone 60 minutes prior to furosemide increases urine output compared with administering metolazone and furosemide concomitantly. Participants will have equal chance of being assigned to each group.
Detailed description
Diuretic resistance is common among patients with acute decompensated heart failure, and one strategy for overcoming this phenomenon is sequential nephron blockade with loop plus thiazide-type diuretics. Metolazone is an oral thiazide-type diuretic commonly used for this purpose. Due to its delayed absorption, some clinicians suggest that metolazone be given 30-60 minutes prior to the loop diuretic. However, the efficacy and safety of such a strategy has not been investigated despite its added complexity. The purpose of this study is to investigate whether pre-dosing with metolazone confers a difference in efficacy and safety compared to administering it at the same time as furosemide.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Prospective, randomized, open-label, active control pilot study
| Arm | Type | Receives |
|---|---|---|
| Metolazone Pre-dosing | Active comparator | Drug: Metolazone 60 minutes prior to furosemideMetolazone 5 mg by mouth administered 60 minutes prior to furosemide background therapy (120 - 160 mg intravenous bolus, followed by furosemide 120 - 160 mg intravenous bolus 12 - 24 hours after) |
| Metolazone Concurrent Dosing | Active comparator | Drug: Metolazone concurrently with furosemideMetolazone 5 mg by mouth administered at the same time as furosemide background therapy (120 - 160 mg intravenous bolus, followed by furosemide 120 - 160 mg intravenous bolus 12 - 24 hours after) |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Admission within 48 hours for acute decompensated heart failure with at least one symptom and one sign of volume overload
- Receipt of loop diuretic prior to admission
- Plan to administer furosemide 120 - 160 mg IV bolus twice daily over the next 24 hours with additional diuresis deemed necessary
- If patient is concurrently administered intravenous vasodilator or inotrope, the dose of vasodilator or inotrope must be stable for 6 hours prior to enrollment with a plan to continue the same dose for the 24 hour duration of this study
Key exclusion criteria (4 listed)
- Metolazone prescribed prior to admission
- Receipt of continuous intravenous infusion of furosemide
- Cirrhosis or end stage renal disease
- Non-English speaking patients
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 |
|---|---|---|
| Metolazone 60 minutes prior to furosemideAlso: ZaroxolynAll patients will receive furosemide background therapy (furosemide 120 - 160 mg IV bolus dosed twice within a twenty four hour period. Patients will be randomized 1:1 to either metolazone 5 mg tablet dosed 60 minutes prior to first dose of furosemide or metolazone dosed concurrently (within ten minute time frame) with the first dose of furosemide. | Drug | Metolazone Pre-dosing |
| Metolazone concurrently with furosemideAlso: ZaroxolynAll patients will receive furosemide background therapy (furosemide 120 - 160 mg IV bolus dosed twice within a twenty four hour period. Patients will be randomized 1:1 to either metolazone 5 mg tablet dosed 60 minutes prior to first dose of furosemide or metolazone dosed concurrently (within ten minute time frame) with the first dose of furosemide. | Drug | Metolazone Concurrent Dosing |
Primary outcome
24-Hour Urine Output
Time frame: 24 hours
Total measured urine output in milliliters produced after metolazone dose is given
6 secondary outcomes
Change in Total Body Weight
Time frame: Baseline and at 12 to 23 hours after metolazone dose
Change in Serum Creatinine
Time frame: Baseline and at 12 to 23 hours after metolazone dose
Acute Kidney Injury
Time frame: Baseline and at 12 to 23 hours after metolazone dose
Hypokalemia
Time frame: Baseline and at 12 to 23 hours after metolazone dose
Hypomagnesemia
Time frame: Baseline and at 12 to 23 hours after metolazone dose
Hyponatremia
Time frame: Baseline and at 12 to 23 hours after metolazone dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 29141174Ellison DH, Felker GM. Diuretic Treatment in Heart Failure. N Engl J Med. 2017 Nov 16;377(20):1964-1975. doi: 10.1056/NEJMra1703100. No abstract available.
- Background: PubMed 21029871Jentzer JC, DeWald TA, Hernandez AF. Combination of loop diuretics with thiazide-type diuretics in heart failure. J Am Coll Cardiol. 2010 Nov 2;56(19):1527-34. doi: 10.1016/j.jacc.2010.06.034.
- Background: PubMed 3793436Grosskopf I, Rabinovitz M, Rosenfeld JB. Combination of furosemide and metolazone in the treatment of severe congestive heart failure. Isr J Med Sci. 1986 Nov;22(11):787-90.
- Background: PubMed 2014951Ellison DH. The physiologic basis of diuretic synergism: its role in treating diuretic resistance. Ann Intern Med. 1991 May 15;114(10):886-94. doi: 10.7326/0003-4819-114-10-886.
- Individual participant dataSharing planned: No
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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.
Brent Reed, PharmD principal investigator
University of Maryland, College Park
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 Metolazone 60 minutes prior to furosemide and Metolazone concurrently with furosemide in people with Fluid Overload and Heart Failure Acute, run by University of Maryland, Baltimore 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 4 inclusion and 4 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 22 Oct 2021. 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 22 Oct 2021). 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?
24-Hour Urine Output (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03746002, which also lists 4 linked publications.
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 22 Oct 2021.