Safety and Efficacy of HA380 Hemoadsorption in Patients With Septic Shock

NCT04997421 | Unknown

• 1 other identifier: T96/2021
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Septic Shock; Acute Kidney Injury

Outcome Measures

Primary Outcomes (3)

• Intensive care mortality

  Intensive care mortality

  During ICU care, 1 year

• 90-day mortality

  90-day mortality

  Within 90 days from ICU admission, 90 days

• Days alive at day 90 without vasoactives, invasive mechanical ventilation and renal replacement therapy.

  Days alive at day 90 without vasoactives, invasive mechanical ventilation and renal replacement therapy.

  90 days following ICU admission, 90 days

Secondary Outcomes (6)

• 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

• 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

• Procalcitonin levels at 24 hours, 48 hours and 72 hours following CVVHDF initiation

  24 hours, 48 hours and 72 hours following CVVHDF initiation

Study Arms (2)

CVVHDF with Oxiris®-AN69 membrane

ACTIVE COMPARATOR

Control arm

Device: Continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes

CVVHDF with Oxiris®-AN69 membrane + Hemoadsorption using HA380

ACTIVE COMPARATOR

Intervention arm

Device: Combined HA380 hemoadsorption and continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes

Interventions

Combined HA380 hemoadsorption and continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes DEVICE

Combined HA380 hemoadsorption and continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes (intervention arm)or mere CVVHDF using the Oxiris®-AN69 membrane (control arm).

CVVHDF with Oxiris®-AN69 membrane + Hemoadsorption using HA380

Continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes DEVICE

Continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes (control arm)

CVVHDF with Oxiris®-AN69 membrane

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Turku University Hospital: lead
• University of Turku: collaborator

Study Sites (1)

Turku University Hospital

Turku, Finland

RECRUITING

MeSH Terms

Conditions

Shock, Septic; Acute Kidney Injury

Interventions

Continuous Renal Replacement Therapy

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Renal Replacement Therapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative

Study Officials

• Mikko J Järvisalo, MD, PhD

  Turku University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mikko J Järvisalo, MD, PhD

CONTACT

+35823130000; mikko.jarvisalo@tyks.fi

Panu Uusalo, MD, PhD

CONTACT

+35823130000; panu.uusalo@tyks.fi

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2021
• First Posted: August 9, 2021
• Study Start: June 10, 2021
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: August 9, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1)