Effects of Hemoadsorption on Vascular Integrity in Septic Shock (ADSORP-VIP Trial): Protocol of a Prospective, Randomised, Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Changes in Syndecan-1 serum levels
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •Patients under 18 years of age and over
- •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).
结局指标
主要结局
Changes in Syndecan-1 serum levels
时间窗: Baseline (T0), 6, 12, 18, and 24 hours, and then daily up to 5 days (including pre- and postadsorbent samples in the CytoSorb group)
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.
次要结局
- Change in Sequential Organ Failure Assessment (SOFA)-2 score(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)(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)(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)(Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0)
- Change from baseline in arterial lactate levels(Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0)
- Change from baseline in procalcitonin concentration(Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0)
- Change from baseline in C-reactive protein concentration(Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0)
- Change from baseline in white blood cell count(Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0)
- Change from baseline in ferritin concentration(Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0)
- Change from baseline in tumor necrosis factor alpha concentration(Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0)
- Change from baseline in interleukin-1 beta concentration(Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0)
- Change from baseline in interleukin-8 concentration(Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0)
- Change from baseline in extravascular Lung Water Index (EVLWI)(Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0)
- Change from baseline in Vasoactive-Inotropic Score (VIS)(Baseline (T0) and 6, 12, 18, 24, 48, 72, 96, and 120 hours after T0)
- Daily fluid balance through Day 28(From T0 through Day 28, assessed every 24 hours)
- Time to first negative daily fluid balance(From T0 through Day 28)
- Cumulative fluid balance through Day 28(From T0 through Day 28, assessed every 24 hours)
- Time to first negative cumulative fluid balance(From T0 through Day 28)
- Vasopressor-free days through Day 28(Day 1 through Day 28)
- Mechanical ventilation-free days through Day 28(Day 1 through Day 28)
- Continuous renal replacement therapy-free days through Day 28(Day 1 through Day 28)
- Intensive Care Unit length of stay through Day 28(From ICU admission through ICU discharge, death in the ICU, or Day 28, whichever occurs first)
- Survival rates (ICU survival, Hospital survival, and 28-day survival)(Up to 28 days.)
- Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)(From baseline up to 28 days.)