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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Septic Shock
• Intervention / Treatment: Procedure: Combined extracorporeal blood purification; Procedure: CRRT

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 14
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Aleksandr Burov; Phone Number: +79854215478; Email: Aleksander.bour@mail.ru
• Study Contact Backup: Name: Gleb Danilov, Phd; Email: gdanilov@nsi.ru

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 125047
    • Recruiting
    • Federal State Autonomous Institution "N .N. Burdenko National Medical Research Center of Neurosurgery" of the Ministry of Healthcare of the Russian Federation
    • Contact: Aleksandr Burov; Phone Number: +79854215478; Email: Aleksander.bour@mail.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial hemorrhagic complication	Presence of any intracranial hemorrhagic complications	in 48 hours after the randomization time
Extracranial hemorrhagic complication	Presence of extracranial hemorrhagic complications	in 48 hours after the randomization time
Death in 28-days after CRRT inititiation	28-days mortality in the observed sample group	28-days after the randomization date
In-hospital death	Hospital mortality in the observed sample group	in 3 months after the randomization date
Albumin blood level reduction	Albumin blood level reduction of more than 10%	24 and 48 hours after the randomization time

Collaborators and Investigators

• Sponsor: Burdenko Neurosurgery Institute
• Investigators: Study Chair: Aleksandr Burov, N. N. Burdenko National Medical Research Center of Neurosurgery

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2018
• Primary Completion (Anticipated): September 10, 2021
• Study Completion (Anticipated): November 10, 2021

Study Registration Dates

• First Submitted: September 21, 2019
• First Submitted That Met QC Criteria: November 1, 2019
• First Posted (Actual): November 5, 2019

Study Record Updates

• Last Update Posted (Actual): September 5, 2021
• Last Update Submitted That Met QC Criteria: August 31, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: septic shock; neurosurgery; cytokine removal; CRRT; blood purification
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Sepsis; Shock, Septic
• Other Study ID Numbers: PPI-2018-06-5

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No