Effects of Hemoadsorption on Vascular Integrity in Septic Shock (ADSORP-VIP)
14. července 2026 aktualizováno: Semmelweis University
Effects of Hemoadsorption on Vascular Integrity in Septic Shock (ADSORP-VIP Trial): Protocol of a Prospective, Randomised, Controlled Trial
This study aims to investigate the effects of adjunctive CytoSorb hemoadsorption therapy versus standard medical treatment on endothelial dysfunction in patients with refractory septic shock.
The investigators hypothesize that hemoadsorption mitigates endothelial and glycocalyx injury by removing inflammatory mediators and other injurious circulating molecules, promoting hemodynamic stabilization.
Přehled studie
Postavení
Postavení
Zatím nenabíráme
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Detailní popis
This is a prospective, randomised, controlled, open-label, monocentric, proof-of-concept trial.
Patients will be randomly assigned in a 1:1 ratio to receive either standard medical therapy alone or standard therapy plus continuous CytoSorb hemoadsorption for 24 hours.
Blood samples will be collected at baseline, 6, 12, 18, and 24 hours, and then daily for 5 days to analyze endothelial markers, microRNAs, and inflammatory parameters.
An adaptive group sequential design allows for an interim unblinded sample size re-estimation after the first 30 evaluable patients.
Typ studie
Typ studie
Intervenční
Zápis (Odhadovaný)
Zápis
110
Fáze
Fáze
- Nelze použít
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní kontakt
Studijní kontakt
- Jméno: Tamás Tóth, Dr.
- Telefonní číslo: +36305399474
- E-mail: tomesz9@gmail.com
Studijní místa
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Budapest, Maďarsko, 1082
- Semmelweis University, Department of Anaesthesiology and Intensive Therapy (Intenzív Terápiás Klinika).
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Kontakt:
- Zsolt Molnár, Prof. Dr.
- Telefonní číslo: +36-1-459-1500
- E-mail: molnar.zsolt1@semmelweis.hu
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Ne
Popis
Inclusion Criteria:
- Septic shock as defined by Sepsis-3 criteria.
- Serum lactate levels >2 and <8 mmol/L at screening.
- Fluid unresponsiveness: Objectively confirmed via dynamic tests or fluid challenges following initial resuscitation.
- Vasopressor Dose Threshold: Norepinephrine base equivalent (NEE) dose > 0.5 µg/kg/min.
- Systemic corticosteroid treatment on board for at least 30 minutes.
- Tissue perfusion impairment: Persistently elevated serum lactate AND/OR prolonged capillary refill time (> 3 seconds) despite standard therapy.
- Alternative causes of shock (e.g., obstructive or cardiogenic) must be ruled out using critical care ultrasonography (CCUS).
- Arterial, central venous catheters and an invasive hemodynamic device (PiCCO, Getinge) in place.
- Inclusion within a maximum of 12 hours after the onset of vasopressor need.
- High likelihood of a dysregulated immune response (PCT ≥ 5 ng/mL AND/OR IL-6 ≥ 1000 pg/mL AND/OR Ferritin ≥ 1000 ng/mL).
- Written informed, retrospective or prospective consent.
Exclusion Criteria:
- Patients under 18 years of age and over 80.
- Unlikely to survive for 24 hours (Moribund).
- Pregnancy.
- SOFA-2 score ≥ 16 at ICU admission.
- Source control is uncertain.
- Thrombocytopenia (<20,000/µL).
- Criteria of standard guideline-based medical treatment not exhausted.
- End-stage organ failure (chronic renal failure (estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2), chronic liver failure (MELD Score >30, ChildPugh score class C.), chronic heart failure (New York Heart Association class IV.); severe chronic pulmonary disease (chronic obstructive pulmonary disease: GOLD D)).
- Expected need to disconnect CytoSorb therapy for more than 2 hours (e.g., surgery, CT transfer).
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Počet zbraní
2
Zbraně a zásahy
Skupina účastníků / ArmSkupina účastníků / Arm |
Intervence / LéčbaIntervence / Léčba |
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Aktivní komparátor: Standard Medical Therapy (Group A)
Patients will receive standard medical therapy (SMT) according to local protocols based on international 'Surviving Sepsis Campaign' guidelines.
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Standard Medical Therapy according to local protocols based on the current international 'Surviving Sepsis Campaign' guidelines.
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Experimentální: CytoSorb Therapy (Group B)
Patients will receive standard medical therapy plus a fixed 24-hour continuous hemoadsorption treatment utilizing two sequential CytoSorb cartridges (exchanged at the 12-hour mark).
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Target blood flow rate of 1.5 ml/kg/min, implemented either as a standalone extracorporeal treatment or integrated into a CRRT circuit (CVVHDF mode, preferably with regional citrate anticoagulation).
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Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Changes in Syndecan-1 serum levels
Časové okno: Baseline (T0), 6, 12, 18, and 24 hours, and then daily up to 5 days (including pre- and postadsorbent samples in the CytoSorb group)
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Serum Syndecan-1, a marker of endothelial glycocalyx injury, will be measured in arterial blood samples.
The outcome is the log-scale change from baseline to the T24 post-baseline Syndecan-1 value in ng/mL.
If the T24 value is missing, the value will be considered missing.
Negative values indicate a decrease from baseline.
Syndecan-1 values will be analysed on the natural logarithmic scale due to expected right skew.
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Baseline (T0), 6, 12, 18, and 24 hours, and then daily up to 5 days (including pre- and postadsorbent samples in the CytoSorb group)
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Sekundární výstupní opatření
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Change in Sequential Organ Failure Assessment (SOFA)-2 score
Časové okno: Baseline (T0), 24 hours, and then daily up to 5 days.
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Sequential Organ Failure Assessment (SOFA)-2 is an organ dysfunction score used in critically ill patients.
SOFA-2 includes 6 organ systems with total score ranging from 0 to 24 (higher scores indicate worse organ dysfunction).
Change from baseline will be calculated at each post-baseline assessment and reported in score points.
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Baseline (T0), 24 hours, and then daily up to 5 days.
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Change from baseline in arterial blood concentrations of endothelial and glycocalyx-specific markers (Glypican-1, Heparan-sulfate, sICAM-1, sVCAM-1, soluble E-selectin, soluble P-selectin)
Časové okno: Baseline (T0), 6, 12, 18, and 24 hours, and then daily up to 5 days.
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Arterial blood concentrations of glypican-1, heparan sulfate, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin/CD62E), and soluble P-selectin (sP-selectin) will be measured in ng/mL.
For each biomarker, the change from baseline (T0) will be calculated at each post-baseline assessment.
Results will be reported separately for each biomarker; no composite score will be calculated.
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Baseline (T0), 6, 12, 18, and 24 hours, and then daily up to 5 days.
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Change from baseline in arterial blood concentrations of endothelial markers (MCP-1, VEGF)
Časové okno: Baseline (T0), 6, 12, 18, and 24 hours, and then daily up to 5 days.
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Arterial blood concentrations of monocyte chemoattractant protein-1/C-C motif chemokine ligand 2 (MCP-1/CCL2) and vascular endothelial growth factor (VEGF) will be measured in pg/mL.
For each biomarker, the change from baseline (T0) will be calculated at each post-baseline assessment.
Results will be reported separately for each biomarker; no composite score will be calculated.
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Baseline (T0), 6, 12, 18, and 24 hours, and then daily up to 5 days.
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Change from baseline in quantification cycle values of selected microRNAs associated with endothelial function, vascular homeostasis, and inflammation (miR-126, miR-92a, miR-155, miR-21, miR-23a)
Časové okno: Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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Expression of miR-126, miR-92a, miR-155, miR-21, and miR-23a will be measured in arterial blood samples by quantitative reverse-transcription polymerase chain reaction and reported as quantification cycle (Cq) values.
For each microRNA, change from baseline at each post-baseline time point will be calculated as the Cq value at that time point minus the corresponding Cq value at baseline (T0).
Results will be analyzed and reported separately for each microRNA; no composite or aggregated microRNA score will be calculated.
Hemolyzed samples will be excluded from the microRNA analyses.
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Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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Change from baseline in arterial lactate levels
Časové okno: Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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Arterial lactate concentration will be measured in arterial blood samples and reported in mmol/L.
at each post-baseline time point will be calculated as the arterial lactate concentration at that time point minus the arterial lactate concentration at baseline (T0).
Changes at each time point will be reported separately.
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Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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Change from baseline in procalcitonin concentration
Časové okno: Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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Procalcitonin (PCT) concentration will be measured in arterial blood samples and reported in ng/mL.
For each participant, change from baseline at each post-baseline time point will be calculated as the PCT concentration at that time point minus the PCT concentration at baseline (T0).
Changes at each time point will be reported separately.
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Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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Change from baseline in C-reactive protein concentration
Časové okno: Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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C-reactive protein (CRP) concentration will be measured in arterial blood samples and reported in mg/L.
For each participant, change from baseline at each post-baseline time point will be calculated as the CRP concentration at that time point minus the CRP concentration at baseline (T0).
Changes at each time point will be reported separately.
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Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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Change from baseline in white blood cell count
Časové okno: Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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White blood cell count (WBC) will be measured in arterial blood samples and reported in G/L.
For each participant, change from baseline at each post-baseline time point will be calculated as the WBC count at that time point minus the WBC count at baseline (T0).
Changes at each time point will be reported separately.
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Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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Change from baseline in ferritin concentration
Časové okno: Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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Ferritin concentration will be measured in arterial blood samples and reported in ng/mL.
For each participant, change from baseline at each post-baseline time point will be calculated as the ferritin concentration at that time point minus the ferritin concentration at baseline (T0).
Changes at each time point will be reported separately.
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Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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Change from baseline in tumor necrosis factor alpha concentration
Časové okno: Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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Tumor necrosis factor alpha (TNF-α) concentration will be measured in arterial blood samples and reported in pg/mL.
For each participant, change from baseline at each post-baseline time point will be calculated as the TNF-α concentration at that time point minus the TNF-α concentration at baseline (T0).
Changes at each time point will be reported separately.
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Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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Change from baseline in interleukin-1 beta concentration
Časové okno: Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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Interleukin-1 beta (IL-1β) concentration will be measured in arterial blood samples and reported in pg/mL.
For each participant, change from baseline at each post-baseline time point will be calculated as the IL-1β concentration at that time point minus the IL-1β concentration at baseline (T0).
Changes at each time point will be reported separately.
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Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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Change from baseline in interleukin-8 concentration
Časové okno: Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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Interleukin-8 (IL-8) concentration will be measured in arterial blood samples and reported in pg/mL.
For each participant, change from baseline at each post-baseline time point will be calculated as the IL-8 concentration at that time point minus the IL-8 concentration at baseline (T0).
Changes at each time point will be reported separately.
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Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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Change from baseline in extravascular Lung Water Index (EVLWI)
Časové okno: Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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Extravascular Lung Water Index willl be measured using invasive hemodynamic monitoring and reported in ml/kg.
Change from baseline at each post-baseline time point will be calculated as the EVLWI at that time point minus the EVLWI at baseline
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Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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Change from baseline in Vasoactive-Inotropic Score (VIS)
Časové okno: Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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The Vasoactive-Inotropic Score (VIS) quantifies the amount of cardiovascular support a patient receives through vasoactive and inotropic medications.
The VIS is calculated as: VIS = dopamine (µg/kg/min) + dobutamine (µg/kg/min) + 100 × epinephrine (µg/kg/min) + 100 × norepinephrine (µg/kg/min) + 10 × milrinone (µg/kg/min) + 10 × vasopressin (U/kg/min) at each time point.
Higher score indicates worse outcome.
VIS at each post-baseline time point will be calculated as the VIS at that time point minus the VIS at baseline (T0).
Changes at each time point will be reported separately.
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Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0
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Daily fluid balance through Day 28
Časové okno: From T0 through Day 28, assessed every 24 hours
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Daily fluid balance will be calculated for each 24-hour period as total fluid intake minus total fluid output.
Negative values indicate that fluid output exceeded fluid intake during the corresponding 24-hour period.
Daily fluid balance will be reported in mL at each assessment day.
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From T0 through Day 28, assessed every 24 hours
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Time to first negative daily fluid balance
Časové okno: From T0 through Day 28
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Time to first negative daily fluid balance will be calculated as the time from T0 to the end of the first 24-hour assessment period during which total fluid output exceeds total fluid intake, corresponding to a daily fluid balance of less than zero.
Time will be reported in days.
Participants who do not achieve a negative daily fluid balance by Day 28 will be censored at Day 28.
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From T0 through Day 28
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Cumulative fluid balance through Day 28
Časové okno: From T0 through Day 28, assessed every 24 hours
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Cumulative fluid balance will be calculated as the sum of fluid intake minus fluid output from T0 through each assessment time point.
Negative values indicate that cumulative fluid output exceeded cumulative fluid intake since T0.
Cumulative fluid balance will be reported in mL at each assessment day.
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From T0 through Day 28, assessed every 24 hours
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Time to first negative cumulative fluid balance
Časové okno: From T0 through Day 28
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Time to first negative cumulative fluid balance will be calculated as the time from T0 to the first assessment at which cumulative fluid output since T0 exceeds cumulative fluid intake since T0, corresponding to a cumulative fluid balance of less than zero.
Time will be reported in days.
Participants who do not achieve a negative cumulative fluid balance by Day 28 will be censored at Day 28.
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From T0 through Day 28
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Vasopressor-free days through Day 28
Časové okno: Day 1 through Day 28
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Vasopressor-free days will be calculated as the number of days from Day 1 through Day 28 during which the participant is alive and free from vasopressor treatment.
A day will be counted as vasopressor-free only when no vasopressor is administered during that day.
The possible range is 0 to 28 days, with higher values indicating more days alive without vasopressor support.
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Day 1 through Day 28
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Mechanical ventilation-free days through Day 28
Časové okno: Day 1 through Day 28
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Mechanical ventilation-free days will be calculated as the number of days from Day 1 through Day 28 during which the participant is alive and free from mechanical ventilation.
A day will be counted as ventilation-free only when no mechanical ventilation is provided during that day.
The possible range is 0 to 28 days, with higher values indicating more days alive without mechanical ventilatory support.
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Day 1 through Day 28
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Continuous renal replacement therapy-free days through Day 28
Časové okno: Day 1 through Day 28
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Continuous renal replacement therapy (CRRT)-free days will be calculated as the number of days from Day 1 through Day 28 during which the participant is alive and free from CRRT.
A day will be counted as CRRT-free only when no CRRT is administered during that day.
The possible range is 0 to 28 days, with higher values indicating more days alive without CRRT.
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Day 1 through Day 28
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Intensive Care Unit length of stay through Day 28
Časové okno: From ICU admission through ICU discharge, death in the ICU, or Day 28, whichever occurs first
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Intensive Care Unit (ICU) length of stay will be calculated as the elapsed time in days from ICU admission to ICU discharge or death in the ICU, whichever occurs first.
Participants who remain in the ICU on Day 28 will be censored at Day 28.
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From ICU admission through ICU discharge, death in the ICU, or Day 28, whichever occurs first
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Survival rates (ICU survival, Hospital survival, and 28-day survival)
Časové okno: Up to 28 days.
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ICU survival, hospital survival, and 28-day survival will be recorded separately as alive/deceased status at ICU discharge, hospital discharge, and Day 28 after randomization.
Results will be reported as proportions of participants surviving at each time point.
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Up to 28 days.
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Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Časové okno: From baseline up to 28 days.
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Adverse events, serious adverse events, and device deficiencies will be recorded from baseline through Day 28.
Events will be summarized by incidence, event type, severity, relationship to the study device or procedure, outcome, and seriousness.
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From baseline up to 28 days.
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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Sponzor
Spolupracovníci
Spolupracovníci
Vyšetřovatelé
Vyšetřovatelé
- Vrchní vyšetřovatel: Zsolt Molnár, Prof. Dr., Department of Anaesthesiology and Intensive Therapy, Semmelweis University, Budapest, Hungary
- Vrchní vyšetřovatel: Péter Hegyi, Prof. Dr., Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Odhadovaný)
Začátek studia
1. září 2026
Primární dokončení (Odhadovaný)
Primární dokončení
1. září 2028
Dokončení studie (Odhadovaný)
Dokončení studie
1. ledna 2029
Termíny zápisu do studia
První předloženo
První předloženo
30. června 2026
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
14. července 2026
První zveřejněno (Aktuální)
První zveřejněno
17. července 2026
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Poslední zveřejněná aktualizace
17. července 2026
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
14. července 2026
Naposledy ověřeno
Naposledy ověřeno
1. června 2026
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
Další identifikační čísla studie
- ADSORP-VIP
- 1158 (Jiný identifikátor: National Registration Number)
- NNGYK/26060-6/2026 (Jiný identifikátor: Hungarian National Centre for Public Health and Pharmacy resolution number)
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Ne
Studuje produkt zařízení regulovaný americkým úřadem FDA
Ne
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .