An interventional study of Natriuresis-guided escalation of loop diuretics in Venous Congestion, Heart Failure Acute and VExUS, sponsored by University Hospital, Akershus. Not yet recruiting at 2 sites in Norway. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-30.
Sponsored by University Hospital, Akershus · Not applicable, Interventional, and Treatment
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.
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.
98 studies on the registry are indexed under Hyperemia; 44 are open to participants now.
This study's planned enrollment of 270 is above the median of 68 across 51 interventional studies indexed under Hyperemia.
Browse Hyperemia studies →University Hospital, Akershus is the lead sponsor of 125 studies on the registry; 28 are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
Standard care, decongestive strategy left at the discretion of the treating physician
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
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.
Time frame: 90 days
Key Secondary Endpoint 1: Difference in win ratio between patients with VExUS grade 3 versus VExUS grade 0-2
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.
Time frame: 90 days
Key Secondary Endpoint 2: Win ratio in patients with VExUS grade 0-2
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.
Time frame: 90 days
90-day time-to-mortality
Difference in survival stratified by VExUS score and intervention group
Time frame: 90 days
90-day time-to-hospitalization
Difference in hospitalization stratified by VExUS score and intervention group
Time frame: 90 days
Hospital length-of-stay
Comparison of hospital length-of-stay between different VExUS score groups and intervention groups
Time frame: 90 days
In-hospital mortality
Assessed as time-to-mortality from date and time of admission measured in hours.
Time frame: From date and time of hospital admission to in-hospital death, censored at time of discharge, assessed up to 30 days
6-month rehospitalization
Time to first hospital readmission (long-term follow-up with registries)
Time frame: 6 months
6-month all-cause mortality
Time to mortality (long-term follow-up with registries)
Time frame: 6 months
Change in patient-reported dyspnea from admission to end of decongestive therapy (7-point Likert scale)
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.
Time frame: 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)
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.
Time frame: 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
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).
Time frame: 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
N-terminal pro-B-type natriuretic peptide value within 24h from discharge or day 7 (whichever occurs first)
Time frame: Pre-discharge (hospital discharge or Day 7, whichever occurs first)
Change in NT-proBNP
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)
Time frame: 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
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).
Time frame: Change in KCCQ Overall Summary Score (0-100) from baseline (admission) to 90 days post-discharge
Change in NYHA class
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).
Time frame: 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
Total administered dose of loop diuretics (mg) during index hospitalization
Time frame: From hospital admission to discharge, assessed up to 7 days
Changes in VExUS score from admission to discharge
In-hospital change in Venous Excess Ultrasound score from admission to discharge,
Time frame: 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
In-hospital change in LMS assessed by FibroScan from admission to discharge.
Time frame: 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
In-hospital change in clinical congestion score from admission to discharge
Time frame: 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
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.
Time frame: Baseline (at hospital admission) and pre-discharge (hospital discharge or Day 7, whichever occurs first), assessed up to 7 days
Plan to share: No — The investigators do not plan to share individual participant data.
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