Acute Heart FailurePhase 4DECONGESTNCT05411991
Diuretic Treatment in Acute Heart Failure With Volume Overload Guided by Serial Spot Urine Sodium Assessment
A Phase 4 study testing UNa measurement after intravenous loop diuretic bolus, Intravenous acetazolamide 500 mg OD and Intravenous bumetanide TID in people with Acute Heart Failure and Diuretics Drug Reactions, run by Vrije Universiteit Brussel at 2 sites in Belgium.
Trial summary
This is a pragmatic, multicenter, interventional, parallel-arm, randomized, open-label trial to investigate whether a diuretic regimen, based on serial assessment of sodium concentration (UNa) on spot urine samples after diuretic administration and with low-threshold use of combination diuretic therapy, improves… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Acute Heart Failure, Diuretics Drug Reactions
- What is being tested?
- UNa measurement after intravenous loop diuretic bolus, Intravenous acetazolamide 500 mg OD and Intravenous bumetanide TID
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 107 participants
- Where
- 2 sitesBelgium
- Study dates
- 12 Jun 2022to 1 Jul 2024
- Phase
- Phase 4
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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At least 18 y/o and able to provide informed consent
- Hospital admission (anticipated stay >24 h after randomisation) with diagnosis of acute heart failure according to the treating physician
- At least one of the following three signs of volume overload:
- bilateral oedema 2+, indicating clear pitting
- ascites that is amenable for drainage, confirmed by echography (no obligation to perform abdominal echocardiography, but necessary when presence of ascites is used as an entry criterion for the study)
- uni- or bilateral pleural effusions that are amenable for drainage, confirmed by chest X-ray or lung ultrasound (no obligation to perform chest X-ray, but necessary when presence of pleural effusions is used as an entry criterion for the study)
- Plasma NTproBNP level >1,000 ng/L
Who cannot join
- No possibility to collect reliable urine spot samples after diuretic administration
- Administration of any diuretic within 6 h before randomisation, except for a mineralocorticoid receptor antagonist or sodium glucose co-transporter-2 inhibitor as part of the patient's maintenance treatment for heart failure. Patients can still be included after withholding these diuretics for 6 h, after which randomisation can be performed if they qualify all other criteria.
- Severe kidney dysfunction, defined as an eGFR <15 mL/min/1.73m² calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula and/or previous, current, or planned future renal replacement therapy
- Systolic blood pressure <90 mmHg, mean arterial pressure <65 mmHg, or need for inotropes/vasopressor therapy at randomisation
- Any acute coronary syndrome within 30 days prior to enrolment, defined as typical chest pain with a troponin rise above the 99th percentile of normal and/or electrocardiographic changes suggestive of cardiac ischemia
- History of heart or kidney transplantation
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- History of mechanical circulatory support
- Known obstructive hypertrophic cardiomyopathy, congenital heart disease, acute mechanical cause of acute heart failure (e.g., papillary muscular rupture), acute myocarditis, or constrictive pericarditis according to the treating physician
- Pregnant or breastfeeding woman
- Concomitant participation in another interventional study
Trial locations and contacts
2 sites in 1 country.
Belgium2 sites
Jessa Hospital
Hasselt, Limburg, 3500
University Hospital Brussels
Jette, Brussels Capital, 1090
About this study
This is a pragmatic, multicenter, interventional, parallel-arm, randomized, open-label trial to investigate whether a diuretic regimen, based on serial assessment of sodium concentration (UNa) on spot urine samples after diuretic administration and with low-threshold use of combination diuretic therapy, improves decongestion versus usual care in acute heart failure (AHF), potentially leading to better clinical outcomes.
Read the detailed description
Key interventions are:
- Assessment of UNa in spot urine samples after every bolus administration of loop diuretics with continuation of intravenous diuretics until resolution of clinical signs of fluid overload AND UNa <80 mmol/L
- Dosing of loop diuretic bolus according to estimated glomerular filtration rate (eGFR)
- Upfront use of intravenous acetazolamide 500 mg OD unless hypernatremia (>145 mmol/L) or metabolic acidosis (bicarbonate <22 mmol/L)
- Upfront use of oral chlorthalidone 50 mg OD if eGFR <30 mL/min/1.73m² OR hypernatremia (>145 mmol/L)
- Switch to full nephron blockade with intravenous acetazolamide 500 mg OD, intravenous bumetanide 4 mg TID, oral chlorthalidone 100 mg OD, and intravenous canrenoate 200 mg OD in case of diuretic resistance, defined as UNa <80 mmol/L and persistent clinical signs of fluid overload
- Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during diuretic therapy with intravenous diuretics
- Conditions
- Acute Heart Failure, Diuretics Drug Reactions
- Being tested
- UNa measurement after intravenous loop diuretic bolus, Intravenous acetazolamide 500 mg OD, Intravenous bumetanide TID, Oral chlorthalidone OD, Intravenous canrenoate 200 mg OD
- Keywords
- Acute Heart Failure, Natriuresis, Diuretics, Edema
- Medical subject headings
- Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UNa measurement after intravenous loop diuretic bolusDiagnostic test
Sodium concentration is measured on a urine spot sample, collected 30-120 min after administration of every protocol-specified intravenous bumetanide dose.
Intravenous acetazolamide 500 mg ODDrug
Also called Diamox (brand name for acetazolamide)
Upfront use of intravenous acetazolamide 500 mg OD as part of the diuretic treatment, unless hypernatremia (>145 mmol/L) or metabolic acidosis (bicarbonate <22 mmol/L) is present at the moment of the scheduled administration.
Intravenous bumetanide TIDDrug
Also called Burinex (brand name for bumetanide)
An intravenous bolus of bumetanide is administered TID, with dosing according to eGFR: 2 mg for an eGFR >45 mL/min/1.73m²; 3 mg for an eGFR 30-45 mL/min/1.73m²; and 4 mg for an eGFR <30 mL/min/1.73m². At any time diuretic resistance is encountered (persistent clinical signs of fluid overload with UNa <80 mmol/L), a dose of 4 mg TID is used.
Oral chlorthalidone ODDrug
Also called Hygroton (brand name for chlorthalidone)
In case of hypernatremia (>145 mmol/L) or low eGFR (<30 mL/min/1.73m²), oral chlorthalidone 50 mg OD is added to the diuretic treatment. At any time diuretic resistance is encountered (persistent clinical signs of fluid overload with UNa <80 mmol/L), oral chlorthalidone is provided at a dose of 100 mg OD. Chlorthalidone is never administered in case of hypotonic hyponatremia with serum sodium concentration <135 mmol/L.
Intravenous canrenoate 200 mg ODDrug
Also called Soldactone (brand name for canrenoate)
At any time diuretic resistance is encountered (persistent clinical signs of fluid overload with UNa <80 mmol/L), intravenous canrenoate 200 mg OD is provided. Canrenoate is never administered in case of hypotonic hyponatremia with serum sodium concentration <135 mmol/L or if serum potassium levels are >5.5 mmol/L. If canrenoate is administered, oral mineralocorticoid receptor drugs are temporarily withhold until switch to oral diuretic treatment.
Maintenance infusionOther
A maintenance infusion with 500 mL dextrose 5% and 3 g MgSO4 is started at an infusion rate of 20 mL/h upon the moment of first protocol-specified administration of intravenous diuretics and continued until switch to oral diuretic therapy. 40 mmol KCl is added if serum potassium levels are <4 mmol/L. In case of hypotonic hyponatremia with serum sodium concentration <130 mmol/L, dextrose 5% will not be provided and MgSO4 will be administered in 50 mL of normal saline (NaCl 0.9%).
Oral potassium supplementsDrug
Also called KCl
If serum potassium levels are <3.5 mmol/L at any time during the administration of intravenous diuretics, oral potassium supplements are provided as needed to keep serum potassium levels >4 mmol/L
Intravenous hypertonic salineOther
In case of hypotonic hyponatremia with serum sodium concentration <125 mmol/L, a bolus of 150 mL hypertonic saline 3% is administered and repeated OD if necessary, until sodium levels are ≥135 mmol/L.
Switch to oral diuretic therapyOther
Upon complete resolution of clinical signs of fluid overload with UNa <80 mmol/L, intravenous diuretics are switched to an oral schedule including:
- Loop diuretics with dose \& frequency at the discretion of the treating physician
- Chlorthalidone 50 mg if added for diuretic resistance at any time during the intravenous diuretic phase
- Spironolactone 25 mg or another equivalent mineralocorticoid receptor antagonist
Usual AHF careOther
It is recommended to administer an intravenous loop diuretic dose at least BID (or through continuous infusion), with the aim of achieving a urine output 3-5 L per day until the patient is considered in an optimal volume status as is recommended by current guidelines.
| Study group | Role | What they receive |
|---|---|---|
| Intervention arm | Experimental | Application of a standardized diuretic schedule with following key components:
* UNa assessment in spot urine sample after every bolus of loop diuretics with continuation of intravenous diuretics until absence of clinical signs of fluid overload AND UNa <80 mmol/L
* Loop diuretic dosing according to estimated glomerular filtration rate (eGFR) with higher dose for lower eGFR
* Upfront use of intravenous acetazolamide 500 mg OD unless hypernatremia or metabolic acidosis
* Upfront use of oral chlorthalidone 50 mg OD if eGFR <30 mL/min/1.73m² OR hypernatremia
* Full nephron blockade with intravenous acetazolamide 500 mg OD, intravenous bumetanide 4 mg TID, oral chlorthalidone 100 mg OD, and intravenous canrenoate 200 mg OD in case of diuretic resistance, defined as UNa <80 mmol/L and persistent clinical signs of fluid overload
* Provision of 500 mL intravenous Dextrose 5% with 3 g MgSO4 and 40 mmol KCl daily during intravenous diuretics Receives: Diagnostic Test: UNa measurement after intravenous loop diuretic bolus; Drug: Intravenous acetazolamide 500 mg OD; Drug: Intravenous bumetanide TID; Drug: Oral chlorthalidone OD; Drug: Intravenous canrenoate 200 mg OD; Other: Maintenance infusion; Drug: Oral potassium supplements; Other: Intravenous hypertonic saline; Other: Switch to oral diuretic therapy |
| Control arm | Active comparator | Usual care for AHF. It is recommended to administer an intravenous loop diuretic dose at least BID (or through continuous infusion), with the aim of achieving a urine output 3-5 L per day until the patient is considered in an optimal volume status as is recommended by current guidelines. Urine electrolyte assessment in the control arm is not allowed as it is a key component of the studied intervention. Receives: Other: Usual AHF care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality, Days in Hospital & Decongestion
The net treatment benefit is calculated for the hierarchical composite primary endpoint. Every patient from the intervention group is pair-wise compared with each patient from the control group to declare a winner or tie. The following criteria are sequentially assessed to declare a winner or a tie:
- Any subject surviving until 30 days after randomization wins from a subject who died. If both subjects did not survive until day 30, there is a tie.
- In a pair of subjects, both surviving up till day 30, the subject with the highest number of days alive and out of hospital or care facility during the 30-day follow-up window is declared the winner.
- In a pair of subjects, both surviving up till day 30 with the same number of days alive and out of hospital/care facility, the subject with the greatest relative reduction in NTproBNP from baseline is the winner (rounded to the closest percentage with a minimal difference of 5%). If the difference is <5%, there is a tie.
Measured: 30 days
Secondary outcomes (9)
Renal Safety Endpoint
Number of patients with doubling of the serum creatinine or plasma cystatin C value compared to baseline with an absolute value >2 mg/dL or >2 mg/L, respectively, or the need for ultrafiltration and/or renal replacement therapy during the index hospital admission.
Measured: 30 days
Hemodynamic Safety Endpoint
Number of patients with a ystolic blood pressure <90 mmHg or mean arterial pressure <65 mmHg or need for vasopressors and/or inotropes during the index hospital admission.
Measured: 30 days
Natriuretic Peptide Change After 30 Days
Relative NT-proBNP change from baseline to 30 days after randomisation [%].
Measured: 30 days
Cancer Antigen 125 (CA125) Change After 30 Days
Relative cancer antigen 125 (CA125) change from baseline to 30 days after randomisation [%].
Measured: 30 days
Number of Participants With Successful Clinical Decongestion
Number of participants with no more than trace edema, absence of jugular venous distension and no rales upon the moment of transition from intravenous diuretics to oral diuretic therapy according to the protocol.
Measured: 30 days
Length of Intravenous Diuretic Therapy
Number of consecutive days from randomization during the index admission on which intravenous diuretic therapy was administered.
Measured: 30 days
Overall Well-being After Decongestion
Five-point Likert scale for overall well-being upon the moment of transition from intravenous diuretics to oral diuretic therapy according to the protocol and compared with the moment of randomisation (5: much improved/4: slightly improved/3: neutral/2: slightly worse/1: much worse).
Measured: 30 days
Length of the Index Hospital Admission
Length of the index hospital admission [days].
Measured: 30 days
Number of Participants Who Are Death, or Have a Non-elective Hospital Admission or Non-elective Medical Contact
Number of participants who are death, or have a non-elective hospital admission or non-elective medical contact
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 posted9 Jun 2022
- Study start12 Jun 2022
- Primary completion1 Jul 2024
- Study completion1 Jul 2024
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 (2)Papers the sponsor has linked to this study.
- 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
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vrije Universiteit Brussel
- Sponsor type
- University, hospital or other
- Collaborators
- Roche Diagnostics GmbH, Jessa Hospital
- Responsible party
- Sponsor
- Investigators
- Frederik H Verbrugge, M.D.; Ph.D.; M.Sc., Principal investigator, Vrije Universiteit Brussel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05411991
- Sponsor's protocol ID
- EC-2021-236
- Other IDs
- 2021-005426-18
- Acronym
- DECONGEST
- Status last verified
- Jul 2025
- First submitted
- 6 Jun 2022
- Last updated
- 11 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD will be made available upon reasonable request in adherence with transparency conventions in medical research and through requests to the chief investigator (Frederik H. Verbrugge, frederik.verbrugge@uzbrussel.be). The executive committee of DECONGEST has developed a comprehensive analysis plan and numerous prespecified analyses, which will be presented in future scientific presentations and publications. At a later time point, the full database will be made available in adherence with the ratified transparency policy.
Publications
Vanhentenrijk S, Verbeeck J, Kalpakos T, Vandoren V, Braeckeveldt L, L'hoyes W, Choustoulakis E, Roosens B, Tang WHW, Verwerft J, Verbrugge FH. Rationale and Design of the DECONGEST (Diuretic Treatment in Acute Heart Failure With Volume Overload Guided by Serial Spot Urine Sodium Assessment) Study. J Card Fail. 2025 Apr;31(4):651-660. doi: 10.1016/j.cardfail.2024.08.044. Epub 2024 Aug 30.
PubMed 39218247Mullens W, Martens P. Contemporary Diuretic Therapies for Acute Heart Failure: Time for a Desalination-Guided Approach? J Card Fail. 2024 May;30(5):737-738. doi: 10.1016/j.cardfail.2024.01.013. Epub 2024 Mar 4. No abstract available.
PubMed 38447632