Clinical trial NCT04997421: Safety and Efficacy of HA380 Hemoadsorption in Patients With Septic Shock
Official title: Safety and Efficacy of HA380 HEMoadsorption in Combination With OXiris Membrane for Continuous HemoDiaFiltration in Patients With Septic Shock - HEMOX-HDF Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Septic Shock
Acute Kidney Injury
Lead sponsor: Turku University Hospital
Sponsor class: OTHER_GOV
Collaborators: name: University of Turku
First posted: 2021-08-09
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection and carries a risk for lethality, considerably exceeding that of a mere 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% despite recent technical advancements in patient care. Sepsis is the leading etiology for AKI and CRRT requirement in ICU patients and almost half of the critically ill patients with sepsis develop AKI.

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. Septic shock is defined according to the Sepsis-3 consensus criteria as sepsis with a vasopressor requirement to maintain a mean blood pressure (MAP) ≥65 mm Hg, despite adequate fluid resuscitation, and a serum lactate level \>2 mmol/L.

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. The aim of these techniques is to decrease the early deleterious effects of the cytokine storm and high endotoxin levels during the first hours and days of treatment of septic shock to benefit the patient. 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 or are under evaluation for improving patient outcomes in septic shock. However, to date the data on outcome benefits remains controversial. Previous study series have shown a decrease in cytokine levels, improved hemodynamics and diminished need for vasopressor in patients treated using these methods. However, mortality benefit remains unclear.

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. To study patients with the highest degree of morbidity the study will recruit only septic shock patients with a high vasopressor requirement before CRRT initiation.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Intensive care mortality
timeFrame: During ICU care, 1 year
measure: 90-day mortality
timeFrame: Within 90 days from ICU admission, 90 days
measure: Days alive at day 90 without vasoactives, invasive mechanical ventilation and renal replacement therapy.
timeFrame: 90 days following ICU admission, 90 days
Secondary outcomes:
measure: Vasopressor support at 24 hours, 48 hours and 72 hours following CVVHDF initiation
timeFrame: 24 hours, 48 hours and 72 hours following CVVHDF initiation
measure: Fluid balance at 24 hours, 48 hours and 72 hours following CVVHDF initiation
timeFrame: 24 hours, 48 hours and 72 hours following CVVHDF initiation
measure: Cytokine levels at 24 hours, 48 hours and 72 hours following CVVHDF initiation
timeFrame: 24 hours, 48 hours and 72 hours following CVVHDF initiation
measure: C-reactive protein levels at 24 hours, 48 hours and 72 hours following CVVHDF initiation
timeFrame: 24 hours, 48 hours and 72 hours following CVVHDF initiation
measure: Procalcitonin levels at 24 hours, 48 hours and 72 hours following CVVHDF initiation
timeFrame: 24 hours, 48 hours and 72 hours following CVVHDF initiation
measure: Renal recovery at 90-days following randomization
timeFrame: 90 days following randomization, 90 days
Other outcomes:
Locations:
city: Turku
country: Finland
facility: Turku University Hospital
Study officials:
affiliation: Turku University Hospital
name: Mikko J Järvisalo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: