Safety and Efficacy of HA380 Hemoadsorption in Patients With Septic Shock

Acute Kidney Injury Clinical Trial

— HEMOX-HDF  

Official title:

Safety and Efficacy of HA380 HEMoadsorption in Combination With OXiris Membrane for Continuous HemoDiaFiltration in Patients With Septic Shock - HEMOX-HDF Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04997421
• Other study ID #: T96/2021
• Status: Recruiting
• Phase: N/A
• Start date: June 10, 2021
• Est. completion date: December 2025

Study information

• Verified date: August 2021
• Source: Turku University Hospital
• Contact: Mikko J Järvisalo, MD, PhD
• Phone: +35823130000
• Email: mikko.jarvisalo[@]tyks.fi
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Septic Shock
• Shock
• Shock, Septic

Intervention

Device:
• Combined HA380 hemoadsorption and continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes
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).
• Continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes
Continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes (control arm)

Locations

Country	Name	City	State
Finland	Turku University Hospital	Turku

Sponsors (2)

Lead Sponsor	Collaborator
Turku University Hospital	University of Turku

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Intensive care mortality	Intensive care mortality	During ICU care, 1 year
Primary	90-day mortality	90-day mortality	Within 90 days from ICU admission, 90 days
Primary	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	Vasopressor support at 24 hours, 48 hours and 72 hours following CVVHDF initiation	Noradrenalin infusion rate (unit:µg/kg/min) at 24 hours, 48 hours and 72 hours following CVVHDF initiation	24 hours, 48 hours and 72 hours following CVVHDF initiation
Secondary	Fluid balance at 24 hours, 48 hours and 72 hours following CVVHDF initiation	Cumulative fluid balance (unit: ml) at 24 hours, 48 hours and 72 hours following CVVHDF initiation	24 hours, 48 hours and 72 hours following CVVHDF initiation
Secondary	Cytokine levels at 24 hours, 48 hours and 72 hours following CVVHDF initiation	Cytokine levels (unit: ng/l) at 24 hours, 48 hours and 72 hours following CVVHDF initiation	24 hours, 48 hours and 72 hours following CVVHDF initiation
Secondary	C-reactive protein levels at 24 hours, 48 hours and 72 hours following CVVHDF initiation	C-reactive protein levels (unit: mg/l) at 24 hours, 48 hours and 72 hours following CVVHDF initiation	24 hours, 48 hours and 72 hours following CVVHDF initiation
Secondary	Procalcitonin levels at 24 hours, 48 hours and 72 hours following CVVHDF initiation	Procalcitonin levels (unit: µg/l) at 24 hours, 48 hours and 72 hours following CVVHDF initiation	24 hours, 48 hours and 72 hours following CVVHDF initiation
Secondary	Renal recovery at 90-days following randomization	Estimated glomerular filtration rate (unit: ml/min/1.73 m²) and dialysis dependency (yes/no) at 90-days following randomization	90 days following randomization, 90 days