Safety and Efficacy of HA380 HEMoadsorption in Combination With OXiris Membrane for Continuous HemoDiaFiltration in Patients With Septic Shock - HEMOX-HDF Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Days alive at day 90 without vasoactives, invasive mechanical ventilation and renal replacement therapy.
研究概览
简要总结
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Intensive care unit (ICU) mortality in patients with septic shock and acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) remains high and approximates 50-60%. Sepsis is the leading etiology for AKI and CRRT requirement in ICU patients.
In septic shock, the dysregulated host response to infectious pathogens leads to a cytokine storm with uncontrolled production and release of humoral pro-inflammatory mediators. These pro-inflammatory mediators and cytokines exert cellular toxicity and promote the development of organ dysfunction and increased mortality.
In addition to treating AKI, CRRT techniques can be employed for adsorption of inflammatory mediators extracorporally using specially developed adsorption membranes, hemoperfusion sorbent cartridges or columns. Several methods and devices, such as Oxiris®-AN69 membrane, CytoSorb® cytokine hemoadsorption and polymyxin B (Toraymyxin) endotoxin adsorption and plasmapheresis have been evaluated in small study series but to date the data on outcome benefits remains controversial.
HA380 (Jafron Biomedical Co , Ltd, Zhuhai, China) is a CE-labeled hemoadsorption cartridge developed to treat patients with septic shock. It contains hemo-compatible, porous polymeric beads that adsorp cytokines and mid-molecular weight toxins on their surface. The cytokines absorved using this cartridge are IL-1, IL-6, IL-8, IL-10 in addition to TNF-α8.
Therefore, this study aims to examine the potential effects of cytokine adsorption using HA380 in addition to hemodiafiltration with the Oxiris®-AN69 membrane on ICU- and 90-day mortality in patients with septic shock and AKI.
详细描述
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection and carries a risk for lethality, considerably exceeding that of a mere infection. Intensive care unit (ICU) mortality in patients with septic shock and acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) remains high and approximates 50-60% despite recent technical advancements in patient care. Sepsis is the leading etiology for AKI and CRRT requirement in ICU patients and almost half of the critically ill patients with sepsis develop AKI.
In septic shock, the dysregulated host response to infectious pathogens leads to a cytokine storm with uncontrolled production and release of humoral pro-inflammatory mediators. These pro-inflammatory mediators and cytokines exert cellular toxicity and promote the development of organ dysfunction and increased mortality. Septic shock is defined according to the Sepsis-3 consensus criteria as sepsis with a vasopressor requirement to maintain a mean blood pressure (MAP) ≥65 mm Hg, despite adequate fluid resuscitation, and a serum lactate level >2 mmol/L.
In addition to treating AKI, CRRT techniques can be employed for adsorption of inflammatory mediators extracorporally using specially developed adsorption membranes, hemoperfusion sorbent cartridges or columns. The aim of these techniques is to decrease the early deleterious effects of the cytokine storm and high endotoxin levels during the first hours and days of treatment of septic shock to benefit the patient. Several methods and devices, such as Oxiris®-AN69 membrane, CytoSorb® cytokine hemoadsorption and polymyxin B (Toraymyxin) endotoxin adsorption and plasmapheresis have been evaluated in small study series or are under evaluation for improving patient outcomes in septic shock. However, to date the data on outcome benefits remains controversial. Previous study series have shown a decrease in cytokine levels, improved hemodynamics and diminished need for vasopressor in patients treated using these methods. However, mortality benefit remains unclear.
HA380 (Jafron Biomedical Co , Ltd, Zhuhai, China) is a CE-labeled hemoadsorption cartridge developed to treat patients with septic shock. It contains hemo-compatible, porous polymeric beads that adsorp cytokines and mid-molecular weight toxins on their surface. The cytokines absorved using this cartridge are IL-1, IL-6, IL-8, IL-10 in addition to TNF-α8.
Therefore, this study aims to examine the potential effects of cytokine adsorption using HA380 in addition to hemodiafiltration with the Oxiris®-AN69 membrane on ICU- and 90-day mortality in patients with septic shock. To study patients with the highest degree of morbidity the study will recruit only septic shock patients with a high vasopressor requirement before CRRT initiation.
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 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >18 years, admitted to the ICU
- •Septic shock according to the Sepsis-3 criteria and a norepinephrine requirement ≥0.2µg/kg/min despite adequate fluid resuscitation
- •Acute kidney injury at or after ICU admission and the treating physician considers that initiation of CRRT is likely within 48 hours.
- •Informed consent from the patient or family members is received
排除标准
- •Maintenance dialysis dependency or RRT during current hospital stay prior to ICU admission
- •GFR less than 20ml/kg/1.73m2 prior to hospital admission (within 365 days)
- •Neurosurgical patients
- •Pregnant women
- •Patient's lack of commitment to start RRT
- •Chronic or acute clinical condition with a prognosis below 6 months
- •History of heparin allergy or heparin induced thrombocytopenia
结局指标
主要结局
Days alive at day 90 without vasoactives, invasive mechanical ventilation and renal replacement therapy.
时间窗: 90 days following ICU admission, 90 days
Days alive at day 90 without vasoactives, invasive mechanical ventilation and renal replacement therapy.
Intensive care mortality
时间窗: During ICU care, 1 year
Intensive care mortality
90-day mortality
时间窗: Within 90 days from ICU admission, 90 days
90-day mortality
次要结局
- Vasopressor support at 24 hours, 48 hours and 72 hours following CVVHDF initiation(24 hours, 48 hours and 72 hours following CVVHDF initiation)
- Fluid balance at 24 hours, 48 hours and 72 hours following CVVHDF initiation(24 hours, 48 hours and 72 hours following CVVHDF initiation)
- Cytokine levels at 24 hours, 48 hours and 72 hours following CVVHDF initiation(24 hours, 48 hours and 72 hours following CVVHDF initiation)
- Renal recovery at 90-days following randomization(90 days following randomization, 90 days)
- Procalcitonin levels at 24 hours, 48 hours and 72 hours following CVVHDF initiation(24 hours, 48 hours and 72 hours following CVVHDF initiation)
- C-reactive protein levels at 24 hours, 48 hours and 72 hours following CVVHDF initiation(24 hours, 48 hours and 72 hours following CVVHDF initiation)