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

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.

Study Overview

• Status: Completed
• Conditions: Acute Heart Failure; Diuretics Drug Reactions
• Intervention / Treatment: 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; Other: Usual AHF care

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

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Brussels
    • Jette, Brussels, Belgium, 1090
      • University Hospital Brussels
  • Limburg
    • Hasselt, Limburg, Belgium, 3500
      • Jessa Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• 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:

  1. bilateral oedema 2+, indicating clear pitting
  2. 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)
  3. 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

Exclusion criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention arm; 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; Sodium concentration is measured on a urine spot sample, collected 30-120 min after administration of every protocol-specified intravenous bumetanide dose.; Drug: Intravenous acetazolamide 500 mg OD; 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.; Other Names: Diamox (brand name for acetazolamide); Drug: Intravenous bumetanide TID; 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.; Other Names: Burinex (brand name for bumetanide); Drug: Oral chlorthalidone OD; 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.; Other Names: Hygroton (brand name for chlorthalidone); Drug: Intravenous canrenoate 200 mg OD; 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.; Other Names: Soldactone (brand name for canrenoate); Other: Maintenance infusion; 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%).; Drug: Oral potassium supplements; 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; Other Names: KCl; Other: Intravenous hypertonic saline; 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.; Other: Switch to oral diuretic therapy; 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
Active Comparator: Control arm; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	30 days
Natriuretic Peptide Change After 30 Days	Relative NT-proBNP change from baseline to 30 days after randomisation [%].	30 days
Cancer Antigen 125 (CA125) Change After 30 Days	Relative cancer antigen 125 (CA125) change from baseline to 30 days after randomisation [%].	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.	30 days
Length of Intravenous Diuretic Therapy	Number of consecutive days from randomization during the index admission on which intravenous diuretic therapy was administered.	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).	30 days
Length of the Index Hospital Admission	Length of the index hospital admission [days].	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	30 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall well-being at discharge	Five point Likert scale for overall well-being upon the moment of hospital discharge for the index hospitalisation and compared with the moment of randomisation (5: much improved/4: slightly improved/3: neutral/2: slightly worse/1: much worse).	30 days
Overall well-being after 30 days	Five point Likert scale for overall well-being 30 days after randomisation and compared with the moment of randomisation (5: much improved/4: slightly improved/3: neutral/2: slightly worse/1: much worse).	30 days
Edema score after decongestion	Edema score (1+: trace; 2+ clear pitting; 3+ clear pitting with visual deformation below the knee; 4+: clear pitting with visual deformation above the knee) upon the moment of transition from intravenous diuretics to oral diuretic therapy according to the protocol.	30 days
Edema score at discharge	Edema score (1+: trace; 2+ clear pitting; 3+ clear pitting with visual deformation below the knee; 4+: clear pitting with visual deformation above the knee) upon the moment of hospital discharge for the index hospitalisation.	30 days
Edema score after 30 days	Edema score (1+: trace; 2+ clear pitting; 3+ clear pitting with visual deformation below the knee; 4+: clear pitting with visual deformation above the knee) 30 days after randomisation.	30 days
Weight change with decongestion	Weight change [kg] from baseline to the moment of transition from intravenous diuretics to oral diuretic therapy according to the protocol.	30 days
Natriuretic peptide change after decongestion	Relative NT-proBNP change from baseline to the moment of transition from intravenous diuretics to oral diuretic therapy according to the protocol [%].	30 days
Cancer antigen 125 (CA125) change after decongestion	Relative cancer antigen 125 (CA125) change from baseline to the moment of transition from intravenous diuretics to oral diuretic therapy according to the protocol [%].	30 days
Change in eGFR after 30 days (serum creatinine-based)	Change in eGFR from randomisation towards 30 days [mL/min/1.73m²] with eGFR calculated according to the Chronic Kidney Disease Epidemiology Collaboration formula with serum creatinine.	30 days
Change in eGFR after 30 days (plasma cystatin C-based)	Change in eGFR from randomisation towards 30 days [mL/min/1.73m²] with eGFR calculated according to the Chronic Kidney Disease Epidemiology Collaboration formula with plasma cystatin C.	30 days
Change in eGFR after 30 days (serum creatinine/plasma cystatin C-based)	Change in eGFR from randomisation towards 30 days [mL/min/1.73m²] with eGFR calculated according to the Chronic Kidney Disease Epidemiology Collaboration formula with serum creatinine and plasma cystatin C.	30 days
Hyperkalemia	Hyperkalemia with serum potassium levels >5.5 mmol/L at any time during the study period.	30 days
Severe hyperkalemia	Severe hyperkalemia with serum potassium levels >6.5 mmol/L at any time during the study period.	30 days
Hypokalemia	Hypokalemia with serum potassium levels <3.5 mmol/L at any time during the study period.	30 days
Hyponatremia	Hyponatremia with serum sodium levels <135 mmol/L at any time during the study period.	30 days
Severe hyponatremia	Severe hyponatremia with serum sodium levels <125 mmol/L at any time during the study period.	30 days
Hypernatremia	Hypernatremia with serum sodium levels >145 mmol/L at any time during the study period.	30 days
Severe metabolic acidosis	Severe metabolic acidosis with serum bicarbonate levels <20 mmol/L at any time during the study period.	30 days
E/e' after decongestion	Averaged medial/lateral E/e' ratio on transthoracic echocardiography upon the moment of transition from intravenous diuretics to oral diuretic therapy according to the protocol.	30 days
E/e' at discharge	Averaged medial/lateral E/e' ratio on transthoracic echocardiography upon the moment of hospital discharge for the index hospitalisation.	30 days
E/e' after 30 days	Averaged medial/lateral E/e' ratio on transthoracic echocardiography 30 days after randomisation.	30 days
Peak left atrial longitudinal strain after decongestion	Peak left atrial longitudinal strain on transthoracic echocardiography upon the moment of transition from intravenous diuretics to oral diuretic therapy according to the protocol.	30 days
Peak left atrial longitudinal strain at discharge	Peak left atrial longitudinal strain on transthoracic echocardiography upon the moment of hospital discharge for the index hospitalisation.	30 days
Peak left atrial longitudinal strain after 30 days	Peak left atrial longitudinal strain on transthoracic echocardiography 30 days after randomisation.	30 days
Tricuspid plane annular excursion over right ventricular systolic pressure (TAPSE/RVSP) ratio after decongestion	TAPSE/RVSP ratio on transthoracic echocardiography upon the moment of transition from intravenous diuretics to oral diuretic therapy according to the protocol.	30 days
TAPSE/RVSP ratio at discharge	TAPSE/RVSP ratio on transthoracic echocardiography upon the moment of hospital discharge for the index hospitalisation.	30 days
TAPSE/RVSP ratio after 30 days	TAPSE/RVSP ratio on transthoracic echocardiography 30 days after randomisation.	30 days
B-lines after decongestion	Number of B-lines on lung ultrasound, scanning 8 thoracic sites upon the moment of transition from intravenous diuretics to oral diuretic therapy according to the protocol.	30 days
B-lines at discharge	Number of B-lines on lung ultrasound, scanning 8 thoracic sites upon the moment of hospital discharge for the index hospitalisation.	30 days
B-lines after 30 days	Number of B-lines on lung ultrasound, scanning 8 thoracic sites 30 days after randomisation.	30 days
VExUS score after decongestion	VExUS score for venous Doppler measurements (0: inferior vena cava diameter <2 cm; 1: inferior vena cava diameter ≥2 cm and normal Doppler measurements; 2: inferior vena cava diameter ≥2 cm and at least 1 severely abnormal* Doppler pattern in the Vv. hepaticae, V. portae or Vv. intrarenalis; 3: inferior vena cava diameter ≥2 cm and at least 2 severely abnormal* Doppler patterns in the Vv. hepaticae, V. portae or Vv. intrarenalis) upon the moment of transition from intravenous diuretics to oral diuretic therapy according to the protocol. *The following Doppler patterns are considered severely abnormal: Vv. Hepaticae: systolic flow reversal V. Portae: >50% pulsatility Vv. Intrarenalis: monophasic diastolic flow	30 days
VExUS score at discharge	VExUS score for venous Doppler measurements (0: inferior vena cava diameter <2 cm; 1: inferior vena cava diameter ≥2 cm and normal Doppler measurements; 2: inferior vena cava diameter ≥2 cm and at least 1 severely abnormal Doppler pattern in the Vv. hepaticae, V. portae or Vv. intrarenalis; 3: inferior vena cava diameter ≥2 cm and at least 2 severely abnormal Doppler patterns in the Vv. hepaticae, V. portae or Vv. intrarenalis) upon the moment of hospital discharge for the index hospitalisation. *The following Doppler patterns are considered severely abnormal: Vv. Hepaticae: systolic flow reversal V. Portae: >50% pulsatility Vv. Intrarenalis: monophasic diastolic flow	30 days
VExUS score after 30 days	VExUS score for venous Doppler measurements (0: inferior vena cava diameter <2 cm; 1: inferior vena cava diameter ≥2 cm and normal Doppler measurements; 2: inferior vena cava diameter ≥2 cm and at least 1 severely abnormal Doppler pattern in the Vv. hepaticae, V. portae or Vv. intrarenalis; 3: inferior vena cava diameter ≥2 cm and at least 2 severely abnormal Doppler patterns in the Vv. hepaticae, V. portae or Vv. intrarenalis) 30 days after randomisation. *The following Doppler patterns are considered severely abnormal: Vv. Hepaticae: systolic flow reversal V. Portae: >50% pulsatility Vv. Intrarenalis: monophasic diastolic flow	30 days

Collaborators and Investigators

• Sponsor: Vrije Universiteit Brussel
• Collaborators: Jessa Hospital; Roche Diagnostics GmbH
• Investigators: Principal Investigator: Frederik H Verbrugge, M.D.; Ph.D.; M.Sc., Vrije Universiteit Brussel

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2022
• Primary Completion (Actual): July 1, 2024
• Study Completion (Actual): July 1, 2024

Study Registration Dates

• First Submitted: June 6, 2022
• First Submitted That Met QC Criteria: June 6, 2022
• First Posted (Actual): June 9, 2022

Study Record Updates

• Last Update Posted (Actual): August 8, 2025
• Last Update Submitted That Met QC Criteria: July 21, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Edema; Diuretics; Natriuresis; Acute Heart Failure
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Chemically-Induced Disorders; Heart Failure; Drug-Related Side Effects and Adverse Reactions; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Membrane Transport Modulators; Natriuretic Agents; Anticonvulsants; Carbonic Anhydrase Inhibitors; Antihypertensive Agents; Sodium Chloride Symporter Inhibitors; Acetazolamide; Bumetanide; Diuretics; Chlorthalidone; Sodium Potassium Chloride Symporter Inhibitors
• Other Study ID Numbers: EC-2021-236; 2021-005426-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No