Safety and Efficiency of Combined Extracorporeal Blood Purification in Neurosurgical ICU. Prospective RCT

Study Overview
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Brief Summary
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To assess the efficiency and safety of combined extracorporeal blood purification in patients with septic shock in Neurosurgical ICU in comparison with the efficiency and safety of the continuous renal replacement therapy (CRRT).

Detailed Description
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According to studies and modern sepsis treatment guidelines, conventional CRRT has not proved effective in the septic shock treatment. Effectiveness of other extracoporeal blood purification methods, such as hemoadsorption or combined blood purification (hemoadsorption combined with CRRT) is widely pointed out in current publications: contemporary studies in general ICU patients demonstrated that the use of hemoadsorption or combined extracorporeal blood purification methods is effective for septic shock patients treatment. It has been proven that cytokines discharged into the systemic blood flow are the key pathophysiological mechanism of septic shock. Hemoadsorption allows for significantly more effective removal of different inflammatory mediators than the traditional methods of CRRT. The combined extracorporeal blood purification method demonstrated similar efficacy in general ICU patients. The aim of this study is to assess the efficiency and safety of combined extracorporeal blood purification in with septic shock in neurosurgical ICU in comparison with the efficiency and safety of the continuous renal replacement therapy (CRRT) with AN69 membrane. Study novelty: We have not encountered published studies evaluating the efficiency of combined extracorporeal blood purification methods in neurosurgical patients with septic shock. Furthermore, currently there is not enough data to compare combined extracorporeal blood purification with CRRT for septic shock treatment. The planned study is the first to investigate the safety and efficiency of combined extracorporeal blood purification in patients with septic shock in neurosurgical ICU.

Official Title
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Pilot Prospective Randomized Controlled Study of Safety and Efficiency of Combined Extracorporeal Blood Purification in Neurosurgical ICU in Comparison With the Continuous Renal Replacement Therapy

Conditions
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Septic Shock

Intervention / Treatment
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* Procedure: Combined extracorporeal blood purification
* Procedure: CRRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of septic shock according to SEPSIS 3 definition Glasgow Coma Scale of 4 and more on admission invasive hemodynamics monitoring norepinephrine > 0,1 µg/kg/min or use of 2 vasopressors Exclusion Criteria: age <18 years >24 hours after diagnosis of septic shock

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combined extracorporeal blood purification<br>CRRT with CVVHDF mode plus treatment with CytSorb adsorber | Procedure: Combined extracorporeal blood purification<br>* Patients receive combined extracorporeal blood purification: CRRT in CVVHDF mode with AN 69 ST set (Baxter) and hemoadsorption with Cytosorbents Corp. CytoSorb adsorber.<br>|
| Active Comparator: Control<br>CRRT with CVVHDF mode | Procedure: CRRT<br>* Patients receive CRRT in CVVHDF mode with AN 69 ST set (Baxter)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vasopressor dose reduction | Vasopressor dose reduction value | 6, 12, 24, 48 and 72 hours after the randomization time | 
| Time on vasopressor support | Time on vasopressor support | Up to 28 days after the randomization date | 
| SOFA score reduction | SOFA score reduction | 24, 48 and 72 hours after the randomization time | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interleukins concentration reduction | Interleukins (IL-1β, IL-6, IL-8, IL-10) concentration reduction | 6, 12, 24 and 48 hours after the randomization time | 
| Tumor necrosis factor-α concentration reduction | Tumor necrosis factor-α concentration reduction | 6, 12, 24 and 48 hours after the randomization time | 
| Total bilirubin concentration reduction | Total bilirubin concentration reduction | 6, 12, 24 and 48 hours after the randomization time | 
| C - reactive protein level reduction | C - reactive protein level reduction | 24, 48 and 72 hours after the randomization time | 
| Procalcitonin concentration reduction | Procalcitonin concentration reduction | 6, 12, 24, 48 and 72 hours after the randomization time | 
| PiCCO-derived parameters normalization | Any PiCCO-derived parameter normalization | 6, 12, 24, 48 and 72 hours after the randomization time | 
| Arteriovenous pCO2 gap reduction | Arteriovenous pCO2 gap reduction | 6, 12, 24, 48 and 72 hours after the randomization time | 
| Arterial blood lactate level reduction | Arterial blood lactate level reduction | 6, 12, 24, 48 and 72 hours after the randomization time | 
| ICU length of stay | ICU length of stay | up to 3 months after the randomization date | 
| Hospital stay time | Hospital stay time | up to 3 months after the randomization date | 
| Mechanical ventilation time | Mechanical ventilation time | up to 3 months after the randomization date | 
| Continuous renal replacement therapy time | Continuous renal replacement therapy time | up to 3 months after the randomization date | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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blood purification, CRRT, septic shock, neurosurgery, cytokine removal