Acute Heart FailurePhase 4P-Value-AHFNCT05986773
Diuretic Strategies in Acute Heart Failure Patients at High Risk for Diuretic Resistance
A Phase 4 study testing Furosemide, Metolazone and Acetazolamide in people with Acute Heart Failure and Diuretic Resistance, run by Stadtspital Zürich at 1 site in Switzerland.
Trial summary
The P-VALUE-AHF trial is a multicenter, randomized, open-label, parallel-group trial on the diuretic and decongestive effects of different diuretic escalation strategies in patients with acute heart failure and diuretic resistance. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Acute Heart Failure, Diuretic Resistance
- What is being tested?
- Furosemide, Metolazone and Acetazolamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteSwitzerland
- Study dates
- 10 Oct 2023to 31 Dec 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Elective or emergency hospital admission with clinical diagnosis of acute heart failure
- One or more clinical signs of volume overload (i.e., peripheral edema, pleural effusion, jugular venous distension)
- Low diuretic efficacy in the first 2 hours after the standard screening dose Furosemide i.v. (i.e., urine volume < 300 ml and urine sodium concentration < 70 mmol/L)
- Plasma N terminal-proBNP level at enrolment > 1000 ng/L
- Signed Informed Consent form
Who cannot join
- Maintenance treatment with Acetazolamide or Metolazone
- Use of any non-protocol defined diuretic agent that cannot be stopped upon study inclusion except for sodium-glucose co-transporter-2 inhibitors (e.g., dapagliflozin, empagliflozin, canagliflozin) and mineralocorticoid receptor antagonists (e.g., spironolactone, eplerenone)
- Systolic blood pressure < 90 mmHg
- Expected use of intravenous vasopressors (e.g., noradrenaline, adrenaline), inotropes (e.g., dobutamine, milrinone, levosimendan) at any time point during the study
- Severe chronic kidney disease (estimated glomerular filtration rate < 15 ml/min/1.73 m2) or use of renal replacement therapy at any time before study inclusion
- Severe liver dysfunction or cirrhosis at risk of hepatic encephalopathy
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- Severe electrolyte disturbances or metabolic acidosis requiring specific intravenous treatment
- Concurrent diagnosis of acute coronary syndrome requiring urgent revascularization
- History of cardiac transplantation or ventricular assist device
- Allergy, intolerance or other contraindication against one of the study drugs
- Pregnancy or breastfeeding
- Age below 18 years.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Diuretic Strategies in Acute Heart Failure Patients at High Risk for Diuretic Resistance (P-Value-AHF): A Multicentre, Randomized, Parallel-group, Open-label Trial
The P-VALUE-AHF trial is a multicenter, randomized, open-label, parallel-group trial on the diuretic and decongestive effects of different diuretic escalation strategies in patients with acute heart failure and diuretic resistance.
The main aims are
- to compare the diuretic efficacy of three therapeutic strategies in patients with acute heart failure and diuretic resistance.
- to assess the improvement in clinical congestion and to compare the symptom-relief among the different treatment regimens
Read the detailed description
The P-VALUE-AHF trial is a multicenter, randomized, open-label, parallel-group trial on the diuretic and decongestive effects of different diuretic escalation strategies in patients with acute heart failure (AHF) and diuretic resistance (DR).
Consenting patients with AHF and DR will be will be randomized towards 3 diuretic regimens. Two to five hours after the initial standard dose Furosemide i.v,
- the first group will receive a doubled dose Furosemide (group FF)
- the second group will receive a combination of standard dose Furosemide and Metolazone (group FM)
- the third group will receive a combination of standard dose Furosemide and Acetazolamide (group FA)
Objectives
- The primary objective is to compare the diuretic efficacy (measured as natriuresis and urine volume) of three therapeutic strategies in patients with acute heart failure and diuretic resistance.
- The secondary objective is to assess the improvement in clinical congestion (EVEREST congestion score) and to compare the symptom-relief (improvement of dyspnoea (VAS)) among the different treatment regimens (FF vs. FM vs. FA).
- Conditions
- Acute Heart Failure, Diuretic Resistance
- Being tested
- Furosemide, Metolazone, Acetazolamide
- Keywords
- Diuretic therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FurosemideDrug
Also called Furosemide, doubled dose
Two to five hours after the initial standard dose Furosemide i.v, the patients are randomized towards 3 study-specific diuretic regimens: the first group will receive a doubled dose Furosemide i.v. (group FF), the second group will receive a combination of standard dose Furosemide i.v. and Metolazone 5 mg p.o. (group FM), the third group will receive a combination of standard dose Furosemide i.v. and Acetazolamide 500 mg i.v. (group FA).
MetolazoneDrug
Also called Furosemide + Metolazone
Two to five hours after the initial standard dose Furosemide i.v, the patients are randomized towards 3 study-specific diuretic regimens: the first group will receive a doubled dose Furosemide i.v. (group FF), the second group will receive a combination of standard dose Furosemide i.v. and Metolazone 5 mg p.o. (group FM), the third group will receive a combination of standard dose Furosemide i.v. and Acetazolamide 500 mg i.v. (group FA).
AcetazolamideDrug
Also called Furosemide + Acetazolamide
Two to five hours after the initial standard dose Furosemide i.v, the patients are randomized towards 3 study-specific diuretic regimens: the first group will receive a doubled dose Furosemide i.v. (group FF), the second group will receive a combination of standard dose Furosemide i.v. and Metolazone 5 mg p.o. (group FM), the third group will receive a combination of standard dose Furosemide i.v. and Acetazolamide 500 mg i.v. (group FA).
| Study group | Role | What they receive |
|---|---|---|
| group FF | Active comparator | Group FF will receive a doubled dose Furosemide i.v.
The first standard dose Furosemide i.v. should be administered according to the current guidelines: (i) diuretic-naïve patients should receive Furosemide 40 mg i.v.; (ii) patients on a maintenance oral diuretic treatment should receive the equivalent dose i.v.
Study medications will be used according to the prescribing information: Furosemide will be administered as an intravenous injection. Receives: Drug: Furosemide |
| group FM | Active comparator | Group FM will receive a combination of standard dose Furosemide i.v. and Metolazone 5 mg p.o.
The first standard dose Furosemide i.v. should be administered according to the current guidelines: (i) diuretic-naïve patients should receive Furosemide 40 mg i.v.; (ii) patients on a maintenance oral diuretic treatment should receive the equivalent dose i.v.
Study medications will be used according to the prescribing information: Furosemide will be administered as an intravenous injection. Metolazone will be administered orally. Receives: Drug: Furosemide; Drug: Metolazone |
| group FA | Active comparator | Group FA will receive a combination of standard dose Furosemide i.v. and Acetazolamide 500 mg i.v.
The first standard dose Furosemide i.v. should be administered according to the current guidelines: (i) diuretic-naïve patients should receive Furosemide 40 mg i.v.; (ii) patients on a maintenance oral diuretic treatment should receive the equivalent dose i.v.
Study medications will be used according to the prescribing information: Furosemide will be administered as an intravenous injection. Acetazolamide (500mg) will be administered intravenously as a short infusion. Receives: Drug: Furosemide; Drug: Acetazolamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diuretic efficacy after 6h
urine- natrium concentration (mmol/L)
Measured: 6 hours after administration of the study-specific diuretic regimen
Secondary outcomes (4)
Diuretic efficacy after 2h
urine- natrium concentration (mmol/L)
Measured: 2 hours after administration of the study-specific diuretic regimen
Diuretic efficacy after 24h
urine- natrium concentration (mmol/L)
Measured: 24 hours after administration of the study-specific diuretic regimen
Change in clinical congestion
EVEREST congestion score
Measured: 0 and 24 hours after administration of the study-specific diuretic regimen
Change in dyspnea severity
numeric rating scale
Measured: 0 and 24 hours after administration of the study-specific diuretic regimen.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2023
- Study start10 Oct 2023
- Primary completion31 Dec 2024
- Study completion31 Dec 2024
Why it stopped: Low recruitment in both centers
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute 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
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stadtspital Zürich
- Sponsor type
- University, hospital or other
- Collaborators
- Ospedale Regionale di Lugano
- Responsible party
- Sponsor
- Investigators
- Mattia Arrigo, PD, Dr. med., Principal investigator, City Hospital Zürich Triemli, Birmensdorferstr. 497, 8063 Zürich, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05986773
- Sponsor's protocol ID
- P-Value-AHF
- Acronym
- P-Value-AHF
- Status last verified
- Dec 2024
- First submitted
- 27 Apr 2023
- Last updated
- 14 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Diuretic Strategies in Acute Heart Failure Patients at High Risk for Diuretic Resistance (P-Value-AHF): A Multicentre, Randomized, Parallel-group, Open-label Trial
- ClinicalTrials.gov ID
- NCT05986773
- Acronym / sponsor ID
- P-Value-AHF / P-Value-AHF
- Conditions
- Acute Heart Failure, Diuretic Resistance
- Keywords
- Diuretic therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low recruitment in both centers
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Stadtspital ZürichUniversity, hospital or other
- Collaborators
- Ospedale Regionale di Lugano
- Study start
- 10 Oct 2023 (actual)
- Primary completion
- 31 Dec 2024 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 14 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The P-VALUE-AHF trial is a multicenter, randomized, open-label, parallel-group trial on the diuretic and decongestive effects of different diuretic escalation strategies in patients with acute heart failure and diuretic resistance.
The main aims are
- to compare the diuretic efficacy of three therapeutic strategies in patients with acute heart failure and diuretic resistance.
- to assess the improvement in clinical congestion and to compare the symptom-relief among the different treatment regimens
Detailed description
The P-VALUE-AHF trial is a multicenter, randomized, open-label, parallel-group trial on the diuretic and decongestive effects of different diuretic escalation strategies in patients with acute heart failure (AHF) and diuretic resistance (DR).
Consenting patients with AHF and DR will be will be randomized towards 3 diuretic regimens. Two to five hours after the initial standard dose Furosemide i.v,
- the first group will receive a doubled dose Furosemide (group FF)
- the second group will receive a combination of standard dose Furosemide and Metolazone (group FM)
- the third group will receive a combination of standard dose Furosemide and Acetazolamide (group FA)
Objectives
- The primary objective is to compare the diuretic efficacy (measured as natriuresis and urine volume) of three therapeutic strategies in patients with acute heart failure and diuretic resistance.
- The secondary objective is to assess the improvement in clinical congestion (EVEREST congestion score) and to compare the symptom-relief (improvement of dyspnoea (VAS)) among the different treatment regimens (FF vs. FM vs. FA).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| group FF | Active comparator | Drug: FurosemideGroup FF will receive a doubled dose Furosemide i.v. The first standard dose Furosemide i.v. should be administered according to the current guidelines: (i) diuretic-naïve patients should receive Furosemide 40 mg i.v.; (ii) patients on a maintenance oral diuretic treatment should receive the equivalent dose i.v. Study medications will be used according to the prescribing information: Furosemide will be administered as an intravenous injection. |
| group FM | Active comparator | Drug: Furosemide, Drug: MetolazoneGroup FM will receive a combination of standard dose Furosemide i.v. and Metolazone 5 mg p.o. The first standard dose Furosemide i.v. should be administered according to the current guidelines: (i) diuretic-naïve patients should receive Furosemide 40 mg i.v.; (ii) patients on a maintenance oral diuretic treatment should receive the equivalent dose i.v. Study medications will be used according to the prescribing information: Furosemide will be administered as an intravenous injection. Metolazone will be administered orally. |
| group FA | Active comparator | Drug: Furosemide, Drug: AcetazolamideGroup FA will receive a combination of standard dose Furosemide i.v. and Acetazolamide 500 mg i.v. The first standard dose Furosemide i.v. should be administered according to the current guidelines: (i) diuretic-naïve patients should receive Furosemide 40 mg i.v.; (ii) patients on a maintenance oral diuretic treatment should receive the equivalent dose i.v. Study medications will be used according to the prescribing information: Furosemide will be administered as an intravenous injection. Acetazolamide (500mg) will be administered intravenously as a short infusion. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Elective or emergency hospital admission with clinical diagnosis of acute heart failure
- One or more clinical signs of volume overload (i.e., peripheral edema, pleural effusion, jugular venous distension)
- Low diuretic efficacy in the first 2 hours after the standard screening dose Furosemide i.v. (i.e., urine volume < 300 ml and urine sodium concentration < 70 mmol/L)
- Plasma N terminal-proBNP level at enrolment > 1000 ng/L
- Signed Informed Consent form
Key exclusion criteria (12 listed)
- Maintenance treatment with Acetazolamide or Metolazone
- Use of any non-protocol defined diuretic agent that cannot be stopped upon study inclusion except for sodium-glucose co-transporter-2 inhibitors (e.g., dapagliflozin, empagliflozin, canagliflozin) and mineralocorticoid receptor antagonists (e.g., spironolactone, eplerenone)
- Systolic blood pressure < 90 mmHg
- Expected use of intravenous vasopressors (e.g., noradrenaline, adrenaline), inotropes (e.g., dobutamine, milrinone, levosimendan) at any time point during the study
- Severe chronic kidney disease (estimated glomerular filtration rate < 15 ml/min/1.73 m2) or use of renal replacement therapy at any time before study inclusion
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 |
|---|---|---|
| FurosemideAlso: Furosemide, doubled doseTwo to five hours after the initial standard dose Furosemide i.v, the patients are randomized towards 3 study-specific diuretic regimens: the first group will receive a doubled dose Furosemide i.v. (group FF), the second group will receive a combination of standard dose Furosemide i.v. and Metolazone 5 mg p.o. (group FM), the third group will receive a combination of standard dose Furosemide i.v. and Acetazolamide 500 mg i.v. (group FA). | Drug | group FA, group FF, group FM |
| MetolazoneAlso: Furosemide + MetolazoneTwo to five hours after the initial standard dose Furosemide i.v, the patients are randomized towards 3 study-specific diuretic regimens: the first group will receive a doubled dose Furosemide i.v. (group FF), the second group will receive a combination of standard dose Furosemide i.v. and Metolazone 5 mg p.o. (group FM), the third group will receive a combination of standard dose Furosemide i.v. and Acetazolamide 500 mg i.v. (group FA). | Drug | group FM |
| AcetazolamideAlso: Furosemide + AcetazolamideTwo to five hours after the initial standard dose Furosemide i.v, the patients are randomized towards 3 study-specific diuretic regimens: the first group will receive a doubled dose Furosemide i.v. (group FF), the second group will receive a combination of standard dose Furosemide i.v. and Metolazone 5 mg p.o. (group FM), the third group will receive a combination of standard dose Furosemide i.v. and Acetazolamide 500 mg i.v. (group FA). | Drug | group FA |
Primary outcome
Diuretic efficacy after 6h
Time frame: 6 hours after administration of the study-specific diuretic regimen
urine- natrium concentration (mmol/L)
4 secondary outcomes
Diuretic efficacy after 2h
Time frame: 2 hours after administration of the study-specific diuretic regimen
Diuretic efficacy after 24h
Time frame: 24 hours after administration of the study-specific diuretic regimen
Change in clinical congestion
Time frame: 0 and 24 hours after administration of the study-specific diuretic regimen
Change in dyspnea severity
Time frame: 0 and 24 hours after administration of the study-specific diuretic regimen.
Results and safety
The study was stopped early (reason given: Low recruitment in both centers). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2025.
- 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.
Mattia Arrigo, PD, Dr. med. principal investigator
City Hospital Zürich Triemli, Birmensdorferstr. 497, 8063 Zürich, Switzerland
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 Furosemide, Metolazone and Acetazolamide in people with Acute Heart Failure and Diuretic Resistance, run by Stadtspital Zürich at 1 site in Switzerland.
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 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: stopped early, as of the sponsor's last update on 14 Feb 2025. 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 Switzerland. 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?
The study was stopped early (reason given: Low recruitment in both centers). Results are not available in the source record.
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?
Diuretic efficacy after 6h (time frame: 6 hours after administration of the study-specific diuretic regimen). 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 14 Feb 2025.