The Role of Blood Purification by Hemoadsorption as Adjunctive Treatment in Children With Septic Shock

NCT05401695 | Completed DMC

• 1 other identifier: Ped Critical Care KCMH
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Sepsis is a major healthcare problem and leading cause of death in the pediatric population. Despite advances in supportive care of critically ill patients, sepsis remains an important cause of death worldwide in children. Overall, sepsis incidence peaked in early childhood. There were an estimated 20.3 million incident sepsis cases worldwide among children younger than 5 years. The Surviving Sepsis Campaign (SSC), which standardized the evidence-base approach to management of septic shock and other sepsis-associated organ dysfunction in children, was recently updated. Nevertheless, mortality and costs are still high. Sepsis is characterized by a complex systemic inflammatory response to a microbial pathogen. A dysregulated host response to infection may result in life-threatening multi-organ dysfunction. Endotoxin, which is found in the outer membrane of Gram-negative bacteria, plays an important role in the pathogenesis of septic shock by producing proinflammatory cytokines. High levels of endotoxin and proinflammatory cytokines are associated with a high mortality rate. Treatment strategies in sepsis and septic shock include early and adequate fluid resuscitation, vasopressors and inotropic support when indicated, early use of broad-spectrum antibiotics with source control, with close monitoring and organ support, if indicated. Other therapies such as immune-modulation and blood purification have been tried to improve outcomes in patients with sepsis and septic shock. Immunomodulation and blood purification techniques aim at restoring the balance of the immune response to infection, by removing the triggers for the response and the cytokines produced and thereby achieve immune homeostasis. Removing endotoxin and inflammatory cytokines would be an effective adjunctive approach in the management of severe sepsis. Direct hemoadsorption (HA) is an extracorporeal technique utilized for blood purification. It involves the passage of blood through an adsorption cartridge, where solutes are removed by direct binding to the sorbent material. Over the years, new adsorption cartridge, with improved characteristics have been developed. Resin-directed hemoadsorption is associated with improved oxygenation, hemodynamic status and cardiac function. However, most studies include only adults, and little information is available regarding the clinical experience and efficacy of blood purification for pediatric septic shock. This pilot study aimed to evaluate the overall clinical outcomes among children who received direct hemoadsorption as an adjunctive treatment for refractory septic shock with high severity scores, compared with outcomes among children admitted to the PICU who received standard treatment.

Conditions

Septic Shock; Multi Organ Failure

Keywords

Blood purification; Hemoperfusion; HA330; PELOD-2 score; PRISM-3 score

Outcome Measures

Primary Outcomes (2)

• The reduction of PELOD-2 score

  The PELOD-2 score, Pediatrics Logistic Organ Dysfunction-2 score as a descriptive scoring system for organ dysfunction. It consists of 10 variables which represent 5 organ dysfunctions. A higher PELOD-2 score correlates with a higher number of organ failures and mortality rate. The minimum of PELOD-2 score is zero, which mortality rate is 0.4%. The higher PELOD-2 score more than 16.8 correlated with mortality rate \>60%.

  At 72 hours after start treatment

• The reduction of PRISM-3 score

  The PRISM-3 score, Pediatrics Risk of Mortality-3 score has 17 physiologic variables subdivided into 26 ranges. Similar to the PELOD-2 score, the higher PRISM-3 score correlates with a higher number of organ failures and mortality rate. The minimum of PRISM-3 score is zero. The maximum PELOD-2 score is 76.

  At 72 hours after start treatment

Secondary Outcomes (8)

• The reduction in IL-6

  At 72 hours after start treatment

• The reduction in VIS at 72 hours

  At 72 hours after start treatment

• The reduction in lactate levels at 72 hours

  At 72 hours after start treatment

• The reduction in oxygenation index at 72 hours

  At 72 hours after start treatment

• The length of PICU stay

  Assessed up to 2 years after PICU admission

Study Arms (2)

The historical control group

NO INTERVENTION

The historical control group was composed of patients treated septic shock between May 2019 and May 2021. They was received routine treatment for septic shock including intravenous fluid resuscitation, antibiotics, removal of source of infection and inotropic drugs within 6 hours after the diagnosis of sepsis.

The HA-treated group

ACTIVE COMPARATOR

The HA-treated group will be enrolled between July 2021 and May 2022. This group included children with sepsis, who were admitted to our PICU during the study period. All children initially received routine treatment for septic shock as the historical control group. An HA330 disposable hemoperfusion cartridge (HA330; Jafron, Zhuhai City, China) was used with a continuous renal replacement therapy (CRRT) machine (Aquarius® or Primaflex®) in this intervention group.

Device: HA330 hemoadsorption technique

Interventions

HA330 hemoadsorption technique DEVICE

Hemoadsorption (HA) treatment An HA330 disposable hemoperfusion cartridge (HA330; Jafron, Zhuhai City, China) was used with a continuous renal replacement therapy (CRRT) machine (Aquarius® or Primaflex®) in the intervention group. We will select a blood circuit for each machine according to the patient's body weight. Vascular access will be established with ultrasound-guided insertion of a double-lumen venous catheter into the right internal jugular or femoral vein. HA will be performed for a maximum of 4 hours, and the second session will be started approximately 24 hours after the end of the first session. The blood flow rate will be started low and be gradually increased while monitoring real-time blood pressure and vital signs with an arterial-line monitor. After the end of the HA session, CRRT will be continued if required.

The HA-treated group

Eligibility Criteria

• Age: 1 Month - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children were 30 days to 15 years of age, who required any dose of at least one vasopressor and one of following
• Pediatric Logistic Organ Dysfunction (PELOD)-2 score ≥ 10
• Pediatric Risk of Mortality (PRISM)-3 score ≥ 15

You may not qualify if:

• Patients receiving end-of-life support
• Patients who uncontrolled bleeding

Sponsors & Collaborators

• Chulalongkorn University: lead

Study Sites (1)

Faculty of Medicine, Chulalongkorn University

Bangkok, 10330, Thailand

Location

MeSH Terms

Conditions

Shock, Septic; Multiple Organ Failure

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: May 7, 2022
• First Posted: June 2, 2022
• Study Start: July 1, 2021
• Primary Completion: April 30, 2022
• Study Completion: April 30, 2022
• Last Updated: June 2, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)