Effects of Hemoadsorption on Vascular Integrity in Septic Shock

Официальное название

Effects of Hemoadsorption on Vascular Integrity in Septic Shock (ADSORP-VIP Trial): Protocol of a Prospective, Randomised, Controlled Trial

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство CytoSorb hemoadsorption
  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).
• Другое Standard Medical Therapy (SMT)
  Standard Medical Therapy according to local protocols based on the current international 'Surviving Sepsis Campaign' guidelines.

Первичные конечные точки

• Changes in Syndecan-1 serum levels [Срок оценки: Baseline (T0), 6, 12, 18, and 24 hours, and then daily up to 5 days (including pre- and postadsorbent samples in the CytoSorb group)]

Вторичные конечные точки (12)

• Change in Sequential Organ Failure Assessment (SOFA)-2 score [Срок оценки: Baseline (T0), 24 hours, and then daily up to 5 days.]
• 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) [Срок оценки: Baseline (T0), 6, 12, 18, and 24 hours, and then daily up to 5 days.]
• Change from baseline in arterial blood concentrations of endothelial markers (MCP-1, VEGF) [Срок оценки: Baseline (T0), 6, 12, 18, and 24 hours, and then daily up to 5 days.]
• 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) [Срок оценки: Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0]
• Change from baseline in arterial lactate levels [Срок оценки: Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0]
• Change from baseline in procalcitonin concentration [Срок оценки: Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0]
• Change from baseline in C-reactive protein concentration [Срок оценки: Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0]
• Change from baseline in white blood cell count [Срок оценки: Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0]
• Change from baseline in ferritin concentration [Срок оценки: Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0]
• Change from baseline in tumor necrosis factor alpha concentration [Срок оценки: Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0]
• Change from baseline in interleukin-1 beta concentration [Срок оценки: Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0]
• Change from baseline in interleukin-8 concentration [Срок оценки: Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Венгрия · 1 центр

• Semmelweis University, Department of Anaesthesiology and Intensive Therapy (Intenzív Teráp — Budapest

Идентификаторы

NCT: NCT07711197 · ADSORP-VIP · 1158 · NNGYK/26060-6/2026

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗