Diuretic Treatment in Acute Heart Failure With Volume Overload Guided by Serial Spot Urine Sodium Assessment

NCT05411991 | Completed Phase 4 Results DMC

• 2 other identifiers: EC-2021-2362021-005426-18
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 2

Brief 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 decongestion versus usual care in acute heart failure (AHF), potentially leading to better clinical outcomes.

Conditions

Acute Heart Failure; Diuretics Drug Reactions

Keywords

Acute Heart Failure; Natriuresis; Diuretics; Edema

Outcome Measures

Primary Outcomes (1)

• 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: 1. 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. 2. 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. 3. 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.

  30 days

Secondary Outcomes (9)

• Renal Safety Endpoint

  30 days

• Hemodynamic Safety Endpoint

  30 days

• Natriuretic Peptide Change After 30 Days

  30 days

• Cancer Antigen 125 (CA125) Change After 30 Days

  30 days

• Number of Participants With Successful Clinical Decongestion

  30 days

Study Arms (2)

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

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.

Other: Usual AHF care

Interventions

UNa measurement after intravenous loop diuretic bolus DIAGNOSTIC_TEST

Sodium concentration is measured on a urine spot sample, collected 30-120 min after administration of every protocol-specified intravenous bumetanide dose.

Intervention arm

Intravenous acetazolamide 500 mg OD DRUG

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.

Also known as: Diamox (brand name for acetazolamide)

Intervention arm

Intravenous bumetanide TID DRUG

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.

Also known as: Burinex (brand name for bumetanide)

Intervention arm

Oral chlorthalidone OD DRUG

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.

Also known as: Hygroton (brand name for chlorthalidone)

Intervention arm

Intravenous canrenoate 200 mg OD DRUG

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.

Also known as: Soldactone (brand name for canrenoate)

Intervention arm

Maintenance infusion OTHER

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%).

Intervention arm

Oral potassium supplements DRUG

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

Also known as: KCl

Intervention arm

Intravenous hypertonic saline OTHER

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.

Intervention arm

Switch to oral diuretic therapy OTHER

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

Intervention arm

Usual AHF care OTHER

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.

Control arm

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Vrije Universiteit Brussel: lead
• Roche Diagnostics GmbH: collaborator
• Jessa Hospital: collaborator

Study Sites (2)

University Hospital Brussels

Jette, Brussels Capital, 1090, Belgium

Location

Jessa Hospital

Hasselt, Limburg, 3500, Belgium

Location

Related Publications (1)

• 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.

  PMID: 39218247 BACKGROUND

MeSH Terms

Conditions

Edema

Interventions

Acetazolamide; Bumetanide; Chlorthalidone; Canrenoic Acid

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfonamides; Amides; meta-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Benzenesulfonamides; Benzophenones; Phthalimides; Imides; Ketones; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Prof. Dr. Frederik H. Verbrugge
• Organization: University Hospital Brussels - Vrije Universiteit Brussel

frederik.verbrugge@uzbrussel.be

024749657

Study Officials

• Frederik H Verbrugge, M.D.; Ph.D.; M.Sc.

  Vrije Universiteit Brussel

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Clinic/Assistant Professor

Study Record Dates

• First Submitted: June 6, 2022
• First Posted: June 9, 2022
• Study Start: June 12, 2022
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2024
• Last Updated: August 8, 2025
• Results First Posted: August 8, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: The study protocol will be shared through clinicaltrials.gov immediately upon release. The statistical analysis plan will be shared before database lock at the end of the study.

Locations

BE (2)