Vexus Assessment and Natriuresis-guided Diuretic Therapy in Acute Heart Failure (VANTAGE-HF)
Studieoversikt
Status
Intervensjon / Behandling
Detaljert beskrivelse
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
Registrering (Antatt)
Fase
- Ikke aktuelt
Kontakter og plasseringer
Studiekontakt
- Navn: Kristian Berge, MD, PhD
- Telefonnummer: +47 41283128
- E-post: kristian.berge@ahus.no
Studer Kontakt Backup
- Navn: Peder L Myhre, MD, PhD
- E-post: p.l.myhre@medisin.uio.no
Studiesteder
-
-
Akershus
-
Lørenskog, Akershus, Norge, 1478
- Akershus University Hospital
-
Ta kontakt med:
- Kristian Berge, MD, PhD
- Telefonnummer: +47 41283128
- E-post: kristian.berge@ahus.no
-
Hovedetterforsker:
- Kristian Berge, MD PhD
-
-
Østfold fylke
-
Sarpsborg, Østfold fylke, Norge, 1714
- Østfold Hospital Trust
-
Ta kontakt med:
- Kristin M Kvakkestad, MD PhD
- Telefonnummer: +47 69860000
- E-post: Kristin.Marie.Kvakkestad@so-hf.no
-
Underetterforsker:
- Kristin M Kvakkestad, MD PhD
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Beskrivelse
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)
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: 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.
|
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.
Andre navn:
|
|
Ingen inngripen: Treatment as usual
Standard care, decongestive strategy left at the discretion of the treating physician
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Win Ratio in patients with VExUS score 3
Tidsramme: 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
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Key Secondary Endpoint 1: Difference in win ratio between patients with VExUS grade 3 versus VExUS grade 0-2
Tidsramme: 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
Tidsramme: 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
|
Andre resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
90-day time-to-mortality
Tidsramme: 90 days
|
Difference in survival stratified by VExUS score and intervention group
|
90 days
|
|
90-day time-to-hospitalization
Tidsramme: 90 days
|
Difference in hospitalization stratified by VExUS score and intervention group
|
90 days
|
|
Hospital length-of-stay
Tidsramme: 90 days
|
Comparison of hospital length-of-stay between different VExUS score groups and intervention groups
|
90 days
|
|
In-hospital mortality
Tidsramme: 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
Tidsramme: 6 months
|
Time to first hospital readmission (long-term follow-up with registries)
|
6 months
|
|
6-month all-cause mortality
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
|
Samarbeidspartnere og etterforskere
Sponsor
Samarbeidspartnere
Studierekorddatoer
Studer hoveddatoer
Studiestart (Antatt)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- 25/11917
- 2026005 (Annet stipend/finansieringsnummer: South-Eastern Norway Regional Health Authority)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
IPD-planbeskrivelse
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .