Vexus Assessment and Natriuresis-guided Diuretic Therapy in Acute Heart Failure

NCT07558798 | Not Yet Recruiting DMC

• 2 other identifiers: 25/119172026005
• Study Type: interventional
• Target: 270
• Locations: 1 country
• Sites: 2

Brief Summary

This study evaluates whether natriuresis-guided diuretic therapy improves outcomes in patients with acute heart failure (AHF) and severe congestion. All patients hospitalized with AHF will be screened using Venous Excess Ultrasound (VExUS) and randomized 1:1 to either natriuresis-guided escalation of loop diuretics or standard care. The primary endpoint, evaluated in patients with VExUS grade 3 (severe congestion), is a hierarchical composite (win ratio) of 90-day mortality, 90-day rehospitalization, and hospital length of stay. Key secondary endpoints (hierarchical) include (1) difference in win ratio between patients with VExUS 3 versus VExUS 0-2 at hospital admission (assessed by interaction testing and statistically tested only if the primary endpoint is significant) and (2) win ratio (primary endpoint) tested among patients with VExUS 0-2 at hospital admission (statistically tested only if the first key seconday endpoint is significant). Exploratory endpoints include in-hospital clinical, hemodynamic, and biochemical outcomes (mortality, eGFR, NT-proBNP, NYHA class, VExUS score, natriuresis/diuresis, and patient-reported dyspnea), associations between congestion markers (VExUS, FibroScan, lung ultrasound, clinical score, and NT-proBNP), as well as quality of life at 90 days, GDMT optimization score at discharge, and long-term time to readmission and mortality assessed through registry linkage.

Conditions

Venous Congestion; Heart Failure Acute; VExUS; Diuretics

Keywords

loop diuretics; heart failure; acute heart failure; vexus; congestion

Outcome Measures

Primary Outcomes (1)

• Win Ratio in patients with VExUS score 3

  Win Ratio of hierarchical composite endpoint (90-day all-cause mortality, 90-day all-cause rehospitalization, and index hospitalization length of stay) comparing natriuresis-guided diuretic therapy versus standard of care in patients with acute heart failure and severe venous congestion (VExUS score 3) at hospital admission.

  90 days

Secondary Outcomes (2)

• Key Secondary Endpoint 1: Difference in win ratio between patients with VExUS grade 3 versus VExUS grade 0-2

  90 days

• Key Secondary Endpoint 2: Win ratio in patients with VExUS grade 0-2

  90 days

Other Outcomes (18)

• 90-day time-to-mortality

  90 days

• 90-day time-to-hospitalization

  90 days

• Hospital length-of-stay

  90 days

Study Arms (2)

Natriuresis-guided decongestion

EXPERIMENTAL

In the intervention arm, intravenous loop diuretics will be administered twice daily, and urinary sodium concentration will be measured two hours after each dose. If urinary sodium is less than 70 mmol/L, the subsequent diuretic dose will be doubled, with additional diuretic agents added if maximum loop diuretic dosing is reached.

Other: Natriuresis-guided escalation of loop diuretics

Treatment as usual

NO INTERVENTION

Standard care, decongestive strategy left at the discretion of the treating physician

Interventions

Natriuresis-guided escalation of loop diuretics OTHER

In the intervention arm, intravenous loop diuretics will be administered twice daily, and urinary sodium concentration will be measured two hours after each dose. If urinary sodium is less than 70 mmol/L, the subsequent diuretic dose will be doubled, with additional diuretic agents added if maximum loop diuretic dosing is reached.

Also known as: Intervention, Natriuresis-guided therapy, Natriuresis-guided decongestion

Natriuresis-guided decongestion

Eligibility Criteria

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

You may qualify if:

• Age \>18 years
• Hospitalization with AHF, either de novo or worsening of chronic HF
• Able to provide written informed consent
• Requirement of intravenous loop diuretic treatment as judged by the treating physician

You may not qualify if:

• Dyspnea primarily due to non-cardiac causes
• Advanced renal disease or estimated glomerular filtration rate (eGFR) \< 20 mL/min/1.73m2 at screening or on-going dialysis.
• Enrollment in another study interfering with the treatment algorithm of the current study
• Inability to follow the treatment protocol
• Language barriers requiring the need for an external interpreter
• Pregnant or nursing (lactating) women
• Very short life expectancy (\<30 days)

Sponsors & Collaborators

• University Hospital, Akershus: lead
• Ostfold Hospital Trust: collaborator

Study Sites (2)

Akershus University Hospital

Lørenskog, Akershus, 1478, Norway

Location

Østfold Hospital Trust

Sarpsborg, Østfold fylke, 1714, Norway

Location

MeSH Terms

Conditions

Hyperemia; Heart Failure

Interventions

Methods

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Heart Diseases

Intervention Hierarchy (Ancestors)

Investigative Techniques

Central Study Contacts

Kristian Berge, MD, PhD

CONTACT

+47 41283128; kristian.berge@ahus.no

Peder L Myhre, MD, PhD

CONTACT

p.l.myhre@medisin.uio.no

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Model Details: VANTAGE-HF uses a parallel-group, 1:1 randomized controlled design with two study arms: natriuresis-guided diuretic therapy (intervention) and standard of care (control). Randomization is stratified using probabilistic minimization (p=0.80) based on six baseline covariates: age, sex, left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE), estimated glomerular filtration rate (eGFR), and NT-proBNP. All patients hospitalized with AHF are screened with VExUS within 24 hours of admission. The primary analysis is restricted to patients with VExUS grade 3 (severe congestion), while patients with VExUS grade 0-2 are enrolled in parallel to enable the key secondary interaction analysis. This enrichment-by-stratification design allows simultaneous evaluation of treatment effect in the pre-specified high-risk subgroup and assessment of whether congestion severity modifies treatment response, without excluding lower-grade patients from the trial.

Study Record Dates

• First Submitted: April 7, 2026
• First Posted: April 30, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

NO (2)