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Vexus Assessment and Natriuresis-guided Diuretic Therapy in Acute Heart Failure (VANTAGE-HF)

23 april 2026 bijgewerkt door: Kristian Berge, University Hospital, Akershus
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.

Studie Overzicht

Toestand

Nog niet aan het werven

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

Heart failure (HF) affects approximately 2% of the general population, and despite advances in medical therapy, outcomes after hospitalization for acute HF (AHF) remain poor. One-year mortality is nearly fourfold higher in hospitalized compared to non-hospitalized HF patients, and more than half require rehospitalization. Residual congestion at discharge is the strongest predictor of adverse outcomes, yet only one in four patients leaves the hospital adequately decongested. Current HF guidelines highlight decongestive strategies as a major evidence gap.

The VANTAGE-HF trial addresses this critical gap by combining two complementary strategies: precision patient stratification using Venous Excess Ultrasound (VExUS) and structured natriuresis-guided titration of loop diuretics. VExUS is a novel, non-invasive ultrasound-based scoring system that significantly improves diagnostic accuracy and severity grading of systemic venous congestion. VExUS score ranges from 0 (no congestion) to 3 (severe congestion), and approximately 40% of hospitalized AHF patients present with VExUS grade 3, a phenotype associated with poor diuretic response and adverse outcomes.

Recent trials have shown that natriuresis-guided diuretic therapy, with stepwise dose escalation if urinary sodium levels remain low, increases the rate of decongestion and reduces hospital length of stay without increasing adverse events. However, these trials were not powered to demonstrate prognostic benefit and did not target specific high-risk subgroups.

All patients admitted with AHF will undergo VExUS assessment within 24 hours of the first administered dose of iv diuretics and will be randomized 1:1 to receive either natriuresis-guided therapy or standard care. 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 including thiazides and/or acetazolamide added if maximum loop diuretic dosing is reached.

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 are tested hierarchically: first, whether the win ratio differs between patients with VExUS grade 3 versus VExUS grade 0-2 at admission (interaction analysis, tested only if the primary endpoint is significant); and second, the win ratio for natriuresis-guided therapy versus standard care in patients with VExUS grade 0-2 (tested only if the first key secondary 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 liver stiffness measurement, lung ultrasound, clinical congestion score, and NT-proBNP), quality of life at 90 days, GDMT optimization score at discharge, and long-term time to readmission and mortality assessed through registry linkage.

The trial has important implications beyond individual patient outcomes. More effective decongestion could shorten hospital stays and prevent rehospitalizations-two key drivers of strain on healthcare systems. By addressing inadequate decongestion, a major source of preventable harm, the trial aims to improve patient outcomes while offering a low-cost, scalable approach that integrates seamlessly into routine clinical workflows.

Studietype

Ingrijpend

Inschrijving (Geschat)

270

Fase

  • Niet toepasbaar

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Contact Back-up

Studie Locaties

  • Noorwegen
    • Akershus
      • Lørenskog, Akershus, Noorwegen, 1478
        • Akershus University Hospital
        • Contact:
        • Hoofdonderzoeker:
          • Kristian Berge, MD PhD
    • Østfold fylke
      • Sarpsborg, Østfold fylke, Noorwegen, 1714
        • Østfold Hospital Trust
        • Contact:
        • Onderonderzoeker:
          • Kristin M Kvakkestad, MD PhD

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Beschrijving

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Natriuresis-guided decongestion
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.
Ander: Natriuresis-guided escalation of loop diuretics
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.
Andere namen:
  • Interventie
  • Natriuresis-guided therapy
  • Natriuresis-guided decongestion
Geen tussenkomst: Treatment as usual
Standard care, decongestive strategy left at the discretion of the treating physician

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Win Ratio in patients with VExUS score 3
Tijdsspanne: 90 days
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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Key Secondary Endpoint 1: Difference in win ratio between patients with VExUS grade 3 versus VExUS grade 0-2
Tijdsspanne: 90 days
Interaction analysis assessing whether the win ratio of the primary composite endpoint (90-day mortality, 90-day rehospitalization, and hospital length of stay) for natriuresis-guided diuretic therapy versus standard of care differs between patients with VExUS grade 3 and patients with VExUS grade 0-2 at hospital admission. Tested only if the primary endpoint is statistically significant.
90 days
Key Secondary Endpoint 2: Win ratio in patients with VExUS grade 0-2
Tijdsspanne: 90 days
Hierarchical composite win ratio of 90-day mortality, 90-day rehospitalization, and hospital length of stay for natriuresis-guided diuretic therapy versus standard of care, assessed in patients with VExUS grade 0-2 at hospital admission. Tested only if Key Secondary Endpoint 1 is statistically significant.
90 days

Andere uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
90-day time-to-mortality
Tijdsspanne: 90 days
Difference in survival stratified by VExUS score and intervention group
90 days
90-day time-to-hospitalization
Tijdsspanne: 90 days
Difference in hospitalization stratified by VExUS score and intervention group
90 days
Hospital length-of-stay
Tijdsspanne: 90 days
Comparison of hospital length-of-stay between different VExUS score groups and intervention groups
90 days
In-hospital mortality
Tijdsspanne: From date and time of hospital admission to in-hospital death, censored at time of discharge, assessed up to 30 days
Assessed as time-to-mortality from date and time of admission measured in hours.
From date and time of hospital admission to in-hospital death, censored at time of discharge, assessed up to 30 days
6-month rehospitalization
Tijdsspanne: 6 months
Time to first hospital readmission (long-term follow-up with registries)
6 months
6-month all-cause mortality
Tijdsspanne: 6 months
Time to mortality (long-term follow-up with registries)
6 months
Change in patient-reported dyspnea from admission to end of decongestive therapy (7-point Likert scale)
Tijdsspanne: From hospital admission to pre-discharge assessment (at hospital discharge or Day 7, whichever occurs first), assessed up to 7 days.
Changes in dyspnea severity from admission to discharge, assessed by a 7-point Likert scale ranging from markedly worse (-3) to markedly better (+3), with 0 indicating no change. Assessed at hospital discharge.
From hospital admission to pre-discharge assessment (at hospital discharge or Day 7, whichever occurs first), assessed up to 7 days.
Change in estimated glomerular filtration rate (eGFR) (delta-value)
Tijdsspanne: Baseline (within 24 hours of hospital admission, including emergency department measurements) and pre-discharge (last day prior to discharge), assessed up to 7 days
In-hospital change in eGFR from admission to discharge. Difference between eGFR measured in the emergency department and the last day before hospital discharge from the index hospitalization.
Baseline (within 24 hours of hospital admission, including emergency department measurements) and pre-discharge (last day prior to discharge), assessed up to 7 days
Guideline-directed medical therapy (GDMT) score
Tijdsspanne: Baseline (at hospital admission, reflecting pre-admission therapy) and pre-discharge (hospital discharge or Day 7, whichever occurs first), assessed up to 7 days
Difference in achieved heart failure GDMT score at discharge (range 0-9), and delta value compared to admission. GDMT score is a composite medication score (range 0-9) assessing optimization of four HF drug classes at discharge. Beta-blockers and ACE inhibitors/ARBs are each scored 0 (not prescribed), 1 (<50% of target daily dose), or 2 (≥50% of target daily dose). ARNI substitution for ACEi/ARB is scored 3. MRA and SGLT2 inhibitor use are each scored 2 (any dose).
Baseline (at hospital admission, reflecting pre-admission therapy) and pre-discharge (hospital discharge or Day 7, whichever occurs first), assessed up to 7 days
Absolute values of NT-proBNP at discharge
Tijdsspanne: Pre-discharge (hospital discharge or Day 7, whichever occurs first)
N-terminal pro-B-type natriuretic peptide value within 24h from discharge or day 7 (whichever occurs first)
Pre-discharge (hospital discharge or Day 7, whichever occurs first)
Change in NT-proBNP
Tijdsspanne: Baseline (within 24 hours of hospital admission) and pre-discharge (hospital discharge or Day 7, whichever occurs first), assessed up to 7 days
In-hospital change (delta value) in N-terminal pro-B-type natriuretic peptide from admission to pre-discharge assessment (<24 hours from discharge or day 7, whichever occurs first)
Baseline (within 24 hours of hospital admission) and pre-discharge (hospital discharge or Day 7, whichever occurs first), assessed up to 7 days
Change in quality of life (KCCQ overall summary score) from baseline assessment to 90 days after discharge
Tijdsspanne: Change in KCCQ Overall Summary Score (0-100) from baseline (admission) to 90 days post-discharge
Quality of life (Kansas City Cardiomyopathy Questionnaire, KCCQ) The KCCQ is a 23-item disease-specific self-administered questionnaire assessing health-related quality of life in patients with heart failure. The Overall Summary Score (range 0-100) integrates physical limitation, symptom frequency and burden, quality of life, and social limitation domains, with higher scores indicating better health status. Assessed at baseline/hospital admission of index hospitalization and at 90 days (telephone visit). Will be assessed as the difference of values (delta values).
Change in KCCQ Overall Summary Score (0-100) from baseline (admission) to 90 days post-discharge
Change in NYHA class
Tijdsspanne: Baseline (at hospital admission) and pre-discharge (hospital discharge or Day 7, whichever occurs first), assessed up to 7 days
New York Heart Association functional class (values 1-4) will be assessed at hospital admission (baseline) and at hospital discharge. Will be assessed as the difference in absolute values (delta value).
Baseline (at hospital admission) and pre-discharge (hospital discharge or Day 7, whichever occurs first), assessed up to 7 days
Total administered dose of loop diuretics (mg) during index hospitalization
Tijdsspanne: From hospital admission to discharge, assessed up to 7 days
Total administered dose of loop diuretics (mg) during index hospitalization
From hospital admission to discharge, assessed up to 7 days
Changes in VExUS score from admission to discharge
Tijdsspanne: Baseline (within 24 hours of hospital admission) and pre-discharge (hospital discharge or Day 7), assessed up to 7 days
In-hospital change in Venous Excess Ultrasound score from admission to discharge,
Baseline (within 24 hours of hospital admission) and pre-discharge (hospital discharge or Day 7), assessed up to 7 days
Changes in LMS assessed by FibroScan from admission to discharge
Tijdsspanne: Baseline (within 24 hours of hospital admission) and pre-discharge (hospital discharge or Day 7, whichever occurs first), assessed up to 7 days
In-hospital change in LMS assessed by FibroScan from admission to discharge.
Baseline (within 24 hours of hospital admission) and pre-discharge (hospital discharge or Day 7, whichever occurs first), assessed up to 7 days
Changes in clinical congestion score from admission to discharge
Tijdsspanne: Baseline (at hospital admission) and pre-discharge (hospital discharge or Day 7, whichever occurs first), assessed up to 7 days
In-hospital change in clinical congestion score from admission to discharge
Baseline (at hospital admission) and pre-discharge (hospital discharge or Day 7, whichever occurs first), assessed up to 7 days
Changes in lung ultrasound congestion score from admission to discharge
Tijdsspanne: Baseline (at hospital admission) and pre-discharge (hospital discharge or Day 7, whichever occurs first), assessed up to 7 days
In-hospital change in lung ultrasound from admission to discharge (hospital discharge or Day 7, whichever occurs first). Eight lung zones are examined (two anterior and two lateral zones per hemithorax). Each zone is scored 0-3 based on B-line pattern: 0 = ≤2 B-lines (normal aeration), 1 = 3-5 discrete B-lines (mild interstitial edema), 2 = ≥5 confluent B-lines (moderate congestion), 3 = white lung or consolidation (severe congestion). Scores are summed to a total of 0-24.
Baseline (at hospital admission) and pre-discharge (hospital discharge or Day 7, whichever occurs first), assessed up to 7 days

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

University Hospital, Akershus

Medewerkers

Ostfold Hospital Trust

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Geschat)

1 april 2026

Primaire voltooiing (Geschat)

1 december 2027

Studie voltooiing (Geschat)

1 juni 2028

Studieregistratiedata

Eerst ingediend

7 april 2026

Eerst ingediend dat voldeed aan de QC-criteria

23 april 2026

Eerst geplaatst (Werkelijk)

30 april 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

30 april 2026

Laatste update ingediend die voldeed aan QC-criteria

23 april 2026

Laatst geverifieerd

1 april 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 25/11917
  • 2026005 (Ander subsidie-/financieringsnummer: South-Eastern Norway Regional Health Authority)

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Beschrijving IPD-plan

The investigators do not plan to share individual participant data.

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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