Acute Decompensated Heart FailurePhase 4AdvorNCT03505788
Acetazolamide in Decompensated Heart Failure With Volume OveRload (ADVOR)
A Phase 4 study testing Acetazolamide in people with Acute Decompensated Heart Failure and Volume Overload, run by Ziekenhuis Oost-Limburg at 1 site in Belgium.
Trial summary
This clinical research study is being conducted in multiple hospitals in Belgium and approximately 519 patients with acute decompensated heart failure are expected to participate. Large-scale research shows that 90% of the physicians treat volume overload with high doses of loop diuretics. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Decompensated Heart Failure, Volume Overload
- What is being tested?
- Acetazolamide
- 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
- 519 participants
- Where
- 1 siteBelgium
- Study dates
- 11 Nov 2018to 16 May 2022
- 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
- Signed written informed consent must be obtained before any study assessment is performed
- Male or female patients 18 years of age or older
- An elective or emergency hospital admission with clinical diagnosis of decompensated HF with at least one clinical sign of volume overload (e.g. oedema (score 2 or more), ascites confirmed by echography or pleural effusion confirmed by chest X-ray or echography)
- Maintenance therapy with oral loop diuretics at a dose of at least 1 mg bumetanide or an equivalent dose for at least 1 month before hospital admission (Conversion: 1 mg bumetanide = 40 mg furosemide = 20 mg torsemide)
- Plasma NT-proBNP levels >1000 ng/mL or BNP levels >250 ng/mL at the time of screening.
- Assessed LVEF by any imaging technique; i.e. echocardiography, catheterization, nuclear scan or magnetic resonance imaging within 12 months of inclusion
Who cannot join
- Concurrent diagnosis of an acute coronary syndrome defined as typical chest pain in addition to a troponin rise above the 99th percentile and/or electrocardiographic changes suggestive of cardiac ischemia
- History of congenital heart disease requiring surgical correction
- History of a cardiac transplantation and/or ventricular assist device
- Systolic blood pressure <90 mmHg or mean arterial pressure <65 mmHg at the moment of admission
- Expected use of intravenous inotropes, vasopressors or nitroprusside during the study. Use of nitrates is allowed only if the patient's systolic blood pressure is >140 mmHg
- Estimated glomerular filtration rate <20 mL/min/1.73m² at screening
Show all 12Show fewer
- Use of renal replacement therapy or ultrafiltration at any time before study inclusion
- Treatment with acetazolamide during the index hospitalization and prior to randomization
- Exposure to nephrotoxic agents (i.e. contrast dye) anticipated within the next 3 days
- Use of any non-protocol defined diuretic agent with the exception of mineralocorticoid receptor antagonists. Thiazides, metolazone, indapamide and amiloride should be stopped upon study inclusion. If patient is taking a combination drug including a thiazide-type diuretic, the thiazide-type diuretic should be stopped
- Current use of sodium-glucose transporter-2 inhibitors
- Subjects who are pregnant or breastfeeding
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Multi-center, Randomized, Double-blind, Phase IV Clinical Trial on the Diuretic Effects of Acetazolamide in Patients With Decompensated Heart Failure and Volume OveRload
This clinical research study is being conducted in multiple hospitals in Belgium and approximately 519 patients with acute decompensated heart failure are expected to participate. Large-scale research shows that 90% of the physicians treat volume overload with high doses of loop diuretics. However, there is not a lot of scientific data available regarding the optimal doses of these diuretic medications. In addition, it is observed that a lot of people, treated with these drugs, are being readmitted to the hospital due to a new episode of heart failure. The hypothesis of this study is that the volume overload could be better treated when patients receive a combination of different types of diuretics. Additionally, the total dose of the administrated diuretics might be lower this way.
Read the detailed description
This is a randomized, double blind study with 2 treatment groups. This means that the patients will be randomized to one of the two treatment groups by chance. Patients randomized to the first group will receive standard treatment with high doses of intravenous loop diuretics and a placebo. Patients randomized to the other treatment group will receive a combination of the same doses of loop diuretics and an additional diuretic, acetazolamide (Diamox®). All diuretics will be administered intravenously. It is expected that the patients of the treatment group with the combination therapy will have a faster reduction of their fluid overload. In consequence the treatment duration and total dose of diuretics administered will be shorter. Acetazolamide (Diamox®) is a diuretic that acts at a different location in the kidney compared to the loop diuretics. This mutual reinforcement will probably reduce the total dose and duration of the diuretics.
The study will start during the hospitalization and will last around 3 months.
- Conditions
- Acute Decompensated Heart Failure, Volume Overload
- Being tested
- Acetazolamide, Placebo
- Medical subject headings
- Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetazolamideDrug
In the experimental group, the patient will receive the standard of care loop diuretics and acetazolamide
PlaceboDrug
In the placebo group, the patient will receive the standard of care loop diuretics and the placebo
| Study group | Role | What they receive |
|---|---|---|
| high-dose loop diuretics+placebo | Placebo comparator | * At the moment of randomization (day 1), oral loop diuretics are stopped and the patient receives IV loop diuretics at a dose equal to the double of his oral daily maintenance dose + 500 mg IV bolus of placebo.
* If the patient still have signs of volume overload the next mornings (day 2 and day 3), the patient will receive IV loop diuretics at a dose equal to the oral daily maintenance dose + 500 mg IV bolus of placebo. It the patient has no sign of volume overload at these time points, the study treatment will be stopped. Receives: Drug: Placebo |
| high-dose loop diuretics+acetazolamide | Experimental | * At the moment of randomization (day 1), oral loop diuretics are stopped and the patient receives IV loop diuretics at a dose equal to the double of his oral daily maintenance dose + 500 mg IV bolus of acetazolamide.
* If the patient still have signs of volume overload the next mornings (day 2 and day 3), the patient will receive IV loop diuretics at a dose equal to the oral daily maintenance dose + 500 mg IV bolus of acetazolamide. It the patient has no sign of volume overload at these time points, the study treatment will be stopped. Receives: Drug: Acetazolamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Successful Decongestion
defined as the absence of signs of volume overload, within 3 days after randomization and with no indication for escalation of decongestive therapy.
Measured: 4 days
Secondary outcomes (4)
Mortality
All-cause mortality during the first 3 months after start of the study
Measured: 3 months
Hospital Readmission
If a patient is readmitted to the hospital within 3 months, this data will be collected
Measured: 3 months
Length of Index Hospital Admission
The time frame between hospital admission and discharge will be calculated
Measured: 3 months
EuroQoL Five Dimensions Questionnaire (EQ-5D)
A questionnaire about the patients' quality of life will be performed at baseline, the morning of day 4, at any readmission, 3 months. The questionnaire is divided into 5 levels of severity with a score varying from 1 to 5. 1 indicates no problems and 5 indicates severe problems. The EQ-5D-5L health status, defined by the EQ-5D-5L descriptive system, are converted into a single index value (utility data). Values are anchored at 1 (full health) and 0 (a state as bad as being dead) as required by their use in economic evaluation. Values less than 0 represent health states regarded as worse than a state that is as bad as being dead.
Measured: at baseline, day 4 (or discharge), at 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2018
- Study start11 Nov 2018
- Primary completion20 Jan 2022
- Study completion16 May 2022
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 (5)Papers the sponsor has linked to this study.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 519 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ziekenhuis Oost-Limburg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wilfried Mullens, Ziekenhuis Oost-Limburg
- Investigators
- Wiflried Mullens, MD PhD, Principal investigator, Ziekenhuis Oost-Limburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03505788
- Sponsor's protocol ID
- ZOLCAR17001
- Acronym
- Advor
- Status last verified
- Aug 2024
- First submitted
- 28 Mar 2018
- Last updated
- 28 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Van den Eynde J, Martens P, Dauw J, Nijst P, Meekers E, Ter Maaten JM, Damman K, Filippatos G, Lassus J, Mebazaa A, Ruschitzka F, Dupont M, Mullens W, Verbrugge FH. Serum Chloride and the Response to Acetazolamide in Patients With Acute Heart Failure and Volume Overload: A Post Hoc Analysis From the ADVOR Trial. Circ Heart Fail. 2024 Oct;17(10):e011749. doi: 10.1161/CIRCHEARTFAILURE.123.011749. Epub 2024 Aug 22.
PubMed 39171394Meekers E, Dauw J, Martens P, Dhont S, Verbrugge FH, Nijst P, Ter Maaten JM, Damman K, Mebazaa A, Filippatos G, Ruschitzka F, Tang WHW, Dupont M, Mullens W. Renal function and decongestion with acetazolamide in acute decompensated heart failure: the ADVOR trial. Eur Heart J. 2023 Oct 1;44(37):3672-3682. doi: 10.1093/eurheartj/ehad557.
PubMed 37623428Verbrugge FH, Martens P, Dauw J, Nijst P, Meekers E, Augusto SN Jr, Ter Maaten JM, Damman K, Filippatos G, Lassus J, Mebazaa A, Ruschitzka F, Dupont M, Mullens W. Natriuretic Response to Acetazolamide in Patients With Acute Heart Failure and Volume Overload. J Am Coll Cardiol. 2023 May 23;81(20):2013-2024. doi: 10.1016/j.jacc.2023.03.400.
PubMed 37197845Martens P, Dauw J, Verbrugge FH, Nijst P, Meekers E, Augusto SN Jr, Ter Maaten JM, Damman K, Mebazaa A, Filippatos G, Ruschitzka F, Tang WHW, Dupont M, Mullens W. Decongestion With Acetazolamide in Acute Decompensated Heart Failure Across the Spectrum of Left Ventricular Ejection Fraction: A Prespecified Analysis From the ADVOR Trial. Circulation. 2023 Jan 17;147(3):201-211. doi: 10.1161/CIRCULATIONAHA.122.062486. Epub 2022 Nov 6.
PubMed 36335479Mullens W, Dauw J, Martens P, Verbrugge FH, Nijst P, Meekers E, Tartaglia K, Chenot F, Moubayed S, Dierckx R, Blouard P, Troisfontaines P, Derthoo D, Smolders W, Bruckers L, Droogne W, Ter Maaten JM, Damman K, Lassus J, Mebazaa A, Filippatos G, Ruschitzka F, Dupont M; ADVOR Study Group. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload. N Engl J Med. 2022 Sep 29;387(13):1185-1195. doi: 10.1056/NEJMoa2203094. Epub 2022 Aug 27.
PubMed 36027559
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Randomized, Double-blind, Phase IV Clinical Trial on the Diuretic Effects of Acetazolamide in Patients With Decompensated Heart Failure and Volume OveRload
- ClinicalTrials.gov ID
- NCT03505788
- Acronym / sponsor ID
- Advor / ZOLCAR17001
- Conditions
- Acute Decompensated Heart Failure, Volume Overload
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 519 participants (actual)
- Lead sponsor
- Ziekenhuis Oost-LimburgUniversity, hospital or other
- Study start
- 11 Nov 2018 (actual)
- Primary completion
- 20 Jan 2022 (actual)
- Study completion
- 16 May 2022 (actual)
- First posted
- 23 Apr 2018 (actual)
- Results
- Posted 28 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical research study is being conducted in multiple hospitals in Belgium and approximately 519 patients with acute decompensated heart failure are expected to participate. Large-scale research shows that 90% of the physicians treat volume overload with high doses of loop diuretics. However, there is not a lot of scientific data available regarding the optimal doses of these diuretic medications. In addition, it is observed that a lot of people, treated with these drugs, are being readmitted to the hospital due to a new episode of heart failure. The hypothesis of this study is that the volume overload could be better treated when patients receive a combination of different types of diuretics. Additionally, the total dose of the administrated diuretics might be lower this way.
Detailed description
This is a randomized, double blind study with 2 treatment groups. This means that the patients will be randomized to one of the two treatment groups by chance. Patients randomized to the first group will receive standard treatment with high doses of intravenous loop diuretics and a placebo. Patients randomized to the other treatment group will receive a combination of the same doses of loop diuretics and an additional diuretic, acetazolamide (Diamox®). All diuretics will be administered intravenously. It is expected that the patients of the treatment group with the combination therapy will have a faster reduction of their fluid overload. In consequence the treatment duration and total dose of diuretics administered will be shorter. Acetazolamide (Diamox®) is a diuretic that acts at a different location in the kidney compared to the loop diuretics. This mutual reinforcement will probably reduce the total dose and duration of the diuretics.
The study will start during the hospitalization and will last around 3 months.
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 |
|---|---|---|
| high-dose loop diuretics+placebo | Placebo comparator | Drug: Placebo* At the moment of randomization (day 1), oral loop diuretics are stopped and the patient receives IV loop diuretics at a dose equal to the double of his oral daily maintenance dose + 500 mg IV bolus of placebo. * If the patient still have signs of volume overload the next mornings (day 2 and day 3), the patient will receive IV loop diuretics at a dose equal to the oral daily maintenance dose + 500 mg IV bolus of placebo. It the patient has no sign of volume overload at these time points, the study treatment will be stopped. |
| high-dose loop diuretics+acetazolamide | Experimental | Drug: Acetazolamide* At the moment of randomization (day 1), oral loop diuretics are stopped and the patient receives IV loop diuretics at a dose equal to the double of his oral daily maintenance dose + 500 mg IV bolus of acetazolamide. * If the patient still have signs of volume overload the next mornings (day 2 and day 3), the patient will receive IV loop diuretics at a dose equal to the oral daily maintenance dose + 500 mg IV bolus of acetazolamide. It the patient has no sign of volume overload at these time points, the study treatment will be stopped. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Signed written informed consent must be obtained before any study assessment is performed
- Male or female patients 18 years of age or older
- An elective or emergency hospital admission with clinical diagnosis of decompensated HF with at least one clinical sign of volume overload (e.g. oedema (score 2 or more), ascites confirmed by echography or pleural effusion confirmed by chest X-ray or echography)
- Maintenance therapy with oral loop diuretics at a dose of at least 1 mg bumetanide or an equivalent dose for at least 1 month before hospital admission (Conversion: 1 mg bumetanide = 40 mg furosemide = 20 mg torsemide)
- Plasma NT-proBNP levels >1000 ng/mL or BNP levels >250 ng/mL at the time of screening.
Key exclusion criteria (12 listed)
- Concurrent diagnosis of an acute coronary syndrome defined as typical chest pain in addition to a troponin rise above the 99th percentile and/or electrocardiographic changes suggestive of cardiac ischemia
- History of congenital heart disease requiring surgical correction
- History of a cardiac transplantation and/or ventricular assist device
- Systolic blood pressure <90 mmHg or mean arterial pressure <65 mmHg at the moment of admission
- Expected use of intravenous inotropes, vasopressors or nitroprusside during the study. Use of nitrates is allowed only if the patient's systolic blood pressure is >140 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 |
|---|---|---|
| AcetazolamideIn the experimental group, the patient will receive the standard of care loop diuretics and acetazolamide | Drug | high-dose loop diuretics+acetazolamide |
| PlaceboIn the placebo group, the patient will receive the standard of care loop diuretics and the placebo | Drug | high-dose loop diuretics+placebo |
Primary outcome
Successful Decongestion
Time frame: 4 days
defined as the absence of signs of volume overload, within 3 days after randomization and with no indication for escalation of decongestive therapy.
4 secondary outcomes
Mortality
Time frame: 3 months
Hospital Readmission
Time frame: 3 months
Length of Index Hospital Admission
Time frame: 3 months
EuroQoL Five Dimensions Questionnaire (EQ-5D)
Time frame: at baseline, day 4 (or discharge), at 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39171394Van den Eynde J, Martens P, Dauw J, Nijst P, Meekers E, Ter Maaten JM, Damman K, Filippatos G, Lassus J, Mebazaa A, Ruschitzka F, Dupont M, Mullens W, Verbrugge FH. Serum Chloride and the Response to Acetazolamide in Patients With Acute Heart Failure and Volume Overload: A Post Hoc Analysis From the ADVOR Trial. Circ Heart Fail. 2024 Oct;17(10):e011749. doi: 10.1161/CIRCHEARTFAILURE.123.011749. Epub 2024 Aug 22.
- Derived from this study: PubMed 37623428Meekers E, Dauw J, Martens P, Dhont S, Verbrugge FH, Nijst P, Ter Maaten JM, Damman K, Mebazaa A, Filippatos G, Ruschitzka F, Tang WHW, Dupont M, Mullens W. Renal function and decongestion with acetazolamide in acute decompensated heart failure: the ADVOR trial. Eur Heart J. 2023 Oct 1;44(37):3672-3682. doi: 10.1093/eurheartj/ehad557.
- Derived from this study: PubMed 37197845Verbrugge FH, Martens P, Dauw J, Nijst P, Meekers E, Augusto SN Jr, Ter Maaten JM, Damman K, Filippatos G, Lassus J, Mebazaa A, Ruschitzka F, Dupont M, Mullens W. Natriuretic Response to Acetazolamide in Patients With Acute Heart Failure and Volume Overload. J Am Coll Cardiol. 2023 May 23;81(20):2013-2024. doi: 10.1016/j.jacc.2023.03.400.
- Derived from this study: PubMed 36335479Martens P, Dauw J, Verbrugge FH, Nijst P, Meekers E, Augusto SN Jr, Ter Maaten JM, Damman K, Mebazaa A, Filippatos G, Ruschitzka F, Tang WHW, Dupont M, Mullens W. Decongestion With Acetazolamide in Acute Decompensated Heart Failure Across the Spectrum of Left Ventricular Ejection Fraction: A Prespecified Analysis From the ADVOR Trial. Circulation. 2023 Jan 17;147(3):201-211. doi: 10.1161/CIRCULATIONAHA.122.062486. Epub 2022 Nov 6.
- Derived from this study: PubMed 36027559Mullens W, Dauw J, Martens P, Verbrugge FH, Nijst P, Meekers E, Tartaglia K, Chenot F, Moubayed S, Dierckx R, Blouard P, Troisfontaines P, Derthoo D, Smolders W, Bruckers L, Droogne W, Ter Maaten JM, Damman K, Lassus J, Mebazaa A, Filippatos G, Ruschitzka F, Dupont M; ADVOR Study Group. Acetazolamide in Acute Decompensated Heart Failure with Volume Overload. N Engl J Med. 2022 Sep 29;387(13):1185-1195. doi: 10.1056/NEJMoa2203094. Epub 2022 Aug 27.
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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.
Wiflried Mullens, MD PhD principal investigator
Ziekenhuis Oost-Limburg
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 Acetazolamide in people with Acute Decompensated Heart Failure and Volume Overload, run by Ziekenhuis Oost-Limburg at 1 site in Belgium.
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 6 inclusion and 12 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: finished, as of the sponsor's last update on 28 Oct 2024. 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 Belgium. 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 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 28 Oct 2024). 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?
Successful Decongestion (time frame: 4 days). 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 NCT03505788, which also lists 5 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 28 Oct 2024.