Hemoadsorpion in Patients With Septic Shock: Efficacy and Safety Evaluation. A Pilot Multicenter Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 76
- 试验地点
- 7
- 主要终点
- SOFA score
研究概览
简要总结
Hemoadsorpion in Patients With Septic Shock: Efficacy and Safety Evaluation. A Pilot Multicenter Randomized Controlled Trial.
The goal of this clinical trial is the estimation of the efficacy and safety of hemoadsorption procedures (LPS (Lipopolysaccharide) and inflammatory mediators adsorption) in participants with septic shock.
The main questions it aims to answer are:
Does hemoadsorption decrease the severity of MODS (multiple organ disfunction syndrome)?
The study will include participants aged 18 to 80 years with a verified diagnosis of septic shock according to SEPSIS 3 criteria, diagnosed within 12 hours, and a SOFA (sequential organ failure assessment) score of 9 or more.
In addition to Standard of Care (SOC), blood purification, including hemoadsorption, will be used. The minimum waiting time after diagnosis of septic shock and initiation of basic therapy before inclusion of the patient in the study therapy is 4 hours.
The choice of procedure will be based on the EAA (Endotoxin Activity Assay) result:
- for an EAA level of 0.6-0.9, selective lipopolysaccharide (LPS) adsorption with duration from 2 to 10 hours;
- for an EAA level less than 0.6, inflammatory mediator adsorption with duration from 6 to 12 hours.
The choice of a specific adsorbers within the LPS and inflammatory mediator adsorption group will be based on randomization.
The use of LPS adsorption is planned based on randomization: Toramyxin R-20 or Efferon LPS. The use of inflammatory mediator adsorption is planned based on randomization: Jafron (HA 330) or CytoSorb.
详细描述
Every participant will receive 2 adsorption procedures. The second procedure will be initiated no later than 24 hours after the initiation of the first procedure.
LPS adsorption will be performed in 38 participants (Efferon LPS in 19 participants and Toramyxin in 19 participants), two procedures per participant.
Inflammatory mediator adsorption will be performed in 38 participants (Jafron HA 330 in 19 participants and CytoSorb in 19 participants), two procedures per participant.
Sample size calculations were performed separately for each treatment cohort. For the endotoxemia cohort (EAA level of 0.6-0.9), this randomized trial is designed to compare Efferron LPS and Toraymyxin with respect to change in SOFA score at 72 hours.
At present, no universally accepted minimal clinically important difference (MCID) has been established for the SOFA score in participants with septic shock. Therefore, the assumed treatment effect was derived from published evidence and expert clinical judgment.
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
- Double (Investigator, Outcomes Assessor)
盲法说明
Double (Investigator, Outcomes Assessor)
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 according to SEPSIS-3 criteria
- •Age: 18-80 years
- •SOFA ≥9 points
- •Diagnosis of septic shock established <12 hours ago
- •Invasive hemodynamic monitoring
- •Norepinephrine dose >0.2 mcg/kg/min
排除标准
- •Absolute neutrophil count less than 500 cells/μL
- •Pregnancy
- •End-stage heart failure (NYHA stage IV)
- •Pulmonary embolism with obstructive shock
- •Ongoing bleeding
- •Atonic coma
- •More than 30 points on the MELD scale, class C on the Child-Pugh scale
- •HIV infection
- •Burns over 10% of the body surface area
- •Patients with oncohematological diseases
- •Patients with a recognized palliative status or the definition of "metastatic cancer"
- •RRT using membranes with a high cutoff point and increased adsorption capacity within 72 hours from the initiation of the first hemoadsorption procedure
- •Use of plasma exchange within 72 hours from the initiation of the first hemoadsorption procedure
研究组 & 干预措施
Inflammatory mediatiors adsorption with Jafron HA 330
Inflammatory mediatiors adsorption with EAA <0,6 with Jafron HA 330
干预措施: Jafron HA 330 (Device)
Endotoxin haemoadsorption with Toramyxin PMX 20R
Endotoxin haemoadsorption with EAA [0.6-0.9] with Toramyxin PMX 20R
干预措施: Toramyxin PMX 20R (Device)
Inflammatory mediatiors adsorption with CytoSorb
Inflammatory mediatiors adsorption with EAA <0,6 with CytoSorb
干预措施: CytoSorb (Device)
Endotoxin haemoadsorption with Efferon LPS
Endotoxin haemoadsorption with EAA [0.6-0.9] with Efferon LPS
干预措施: Efferon LPS (Device)
结局指标
主要结局
SOFA score
时间窗: Assessed at 72 hours after hemoadsorption initiation
MODS dynamics majored by SOFA (sequential organ failure assessment) score
SOFA (sequential organ failure assessment) score
时间窗: Assessed at 72 hours after hemoadsorption initiation
MODS (multiple organ disfunction syndrome) dynamics majored by SOFA (sequential organ failure assessment) score. SOFA score ranges from 0 (best) to 24 (worst) points.
次要结局
- VIS dynamics(Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- NE dose dynamics(Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- Direct bilirubin level dynamics(Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- MAP/VIS dynamics(Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- P/f ratio dynamics(Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- Lactate level dynamics(Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- Total bilirubin level dynamics(Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- Indirect bilirubin level dynamics(Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- Ferritin level dynamics(Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- PCT level dynamics(Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- CRP level dynamics(Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- NLR dynamics(Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- PLR dynamics(Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- TNF level dynamics(Assessed at 3 time points: before hemoadsorption initiation (baseline); 48 hours and 72 hours after hemoadsorption initiation)
- IL 6 level dynamics(Assessed at 3 time points: before hemoadsorption initiation (baseline); 48 hours and 72 hours after hemoadsorption initiation)
- IL 10 level dynamics(Time Frame: Assessed at 3 time points: before hemoadsorption initiation (baseline); 48 hours and 72 hours after hemoadsorption initiation)
- 28 - days mortality(Will be calculated for 28 days after hemoadsorption initiation)
- 90 - days mortality(Will be calculated for 90 days after hemoadsorption initiation)
- SOFA dynamics(Assessed at 4 time points: before hemoadsorption initiatioin (baseline); at 24, 48 and 120 hours after hemoadsorption initiation)
- SOFA 2 dynamics(Assessed at 5 time points: before hemoadsorption initiatioin (baseline); at 24, 48, 72 and 120 hours after hemoadsorption initiation)
- Vasoactive Inotropic Score (VIS) dynamics(Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- Norepinephrine dose dynamics(Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- Hemodynamic index dynamics(Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- Horowitz index dynamics(Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- Procalcitonin (PCT) level dynamics(Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- C- reactive protein (CRP) level dynamics(Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- NLR (neutrophil-to-lymphocyte ratio) dynamics(Time Frame: Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- PLR (Platelet-to-lymphocyte ratio) dynamics(Assessed at 4 time points: before hemoadsorption initiation (baseline); 24 hours, 48 hours and 72 hours after hemoadsorption initiation)
- TNF (Tumor necrosis factor-alpha) level dynamics(Assessed at 3 time points: before hemoadsorption initiation (baseline); 48 hours and 72 hours after hemoadsorption initiation)
- IL 6 (Interleukin 6) level dynamics(Assessed at 3 time points: before hemoadsorption initiation (baseline); 48 hours and 72 hours after hemoadsorption initiation)
- IL 10 (Interleukin 10) level dynamics(Time Frame: Assessed at 3 time points: before hemoadsorption initiation (baseline); 48 hours and 72 hours after hemoadsorption initiation)
- SOFA (sequential organ failure assessment) dynamics(Assessed at 4 time points: before hemoadsorption initiatioin (baseline); at 24, 48 and 120 hours after hemoadsorption initiation)
- SOFA 2 (sequential organ failure assessment) dynamics(Assessed at 5 time points: before hemoadsorption initiatioin (baseline); at 24, 48, 72 and 120 hours after hemoadsorption initiation)