Septic ShockHEMOX-HDFNCT04997421
Safety and Efficacy of HA380 Hemoadsorption in Patients With Septic Shock
A study testing Combined HA380 hemoadsorption and continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes and Continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes in people with Septic Shock and Acute Kidney Injury, run by Turku University Hospital at 1 site in Finland.
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%. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Septic Shock, Acute Kidney Injury
- What is being tested?
- Combined HA380 hemoadsorption and continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes and Continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteFinland
- Study dates
- 10 Jun 2021to Dec 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 79 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Finland1 site, 1 recruiting
- Recruiting
Turku University Hospital
Turku
Mikko J Järvisalo, MD, PhD, +35823130000, mikko.jarvisalo@tyks.fi
Panu Uusalo, MD, PhD, +35823130000, panu.uusalo@tyks.fi
About this study
Official title: Safety and Efficacy of HA380 HEMoadsorption in Combination With OXiris Membrane for Continuous HemoDiaFiltration in Patients With Septic Shock - HEMOX-HDF Trial
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.
Read more
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.
Read the 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.
- Conditions
- Septic Shock, Acute Kidney Injury
- Being tested
- Combined HA380 hemoadsorption and continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes, Continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes
- Medical subject headings
- Shock, Septic, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combined HA380 hemoadsorption and continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranesDevice
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 membranesDevice
Continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes (control arm)
| Study group | Role | What they receive |
|---|---|---|
| CVVHDF with Oxiris®-AN69 membrane | Active comparator | Control arm Receives: Device: Continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes |
| CVVHDF with Oxiris®-AN69 membrane + Hemoadsorption using HA380 | Active comparator | Intervention arm Receives: Device: Combined HA380 hemoadsorption and continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Intensive care mortality
Intensive care mortality
Measured: During ICU care, 1 year
90-day mortality
90-day mortality
Measured: 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.
Measured: 90 days following ICU admission, 90 days
Secondary outcomes (6)
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
Measured: 24 hours, 48 hours and 72 hours following CVVHDF initiation
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
Measured: 24 hours, 48 hours and 72 hours following CVVHDF initiation
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
Measured: 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
C-reactive protein levels (unit: mg/l) at 24 hours, 48 hours and 72 hours following CVVHDF initiation
Measured: 24 hours, 48 hours and 72 hours following CVVHDF initiation
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
Measured: 24 hours, 48 hours and 72 hours following CVVHDF initiation
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
Measured: 90 days following randomization, 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2021
- Study start10 Jun 2021
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- More trials run by Turku University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Turku University Hospital
- Sponsor type
- Other government
- Collaborators
- University of Turku
- Responsible party
- Sponsor
- Investigators
- Mikko J Järvisalo, MD, PhD, Principal investigator, Turku University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04997421
- Sponsor's protocol ID
- T96/2021
- Acronym
- HEMOX-HDF
- Status last verified
- Aug 2021
- First submitted
- 21 Jun 2021
- Last updated
- 9 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of HA380 HEMoadsorption in Combination With OXiris Membrane for Continuous HemoDiaFiltration in Patients With Septic Shock - HEMOX-HDF Trial
- ClinicalTrials.gov ID
- NCT04997421
- Acronym / sponsor ID
- HEMOX-HDF / T96/2021
- Conditions
- Septic Shock, Acute Kidney Injury
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Turku University HospitalOther government
- Collaborators
- University of Turku
- Study start
- 10 Jun 2021 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 9 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CVVHDF with Oxiris®-AN69 membrane | Active comparator | Device: Continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranesControl arm |
| CVVHDF with Oxiris®-AN69 membrane + Hemoadsorption using HA380 | Active comparator | Device: Combined HA380 hemoadsorption and continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranesIntervention arm |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Combined HA380 hemoadsorption and continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranesCombined HA380 hemoadsorption and continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes (intervention arm)or mere CVVHDF using the Oxiris®-AN69 membrane (control arm). | Device | CVVHDF with Oxiris®-AN69 membrane + Hemoadsorption using HA380 |
| Continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranesContinuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes (control arm) | Device | CVVHDF with Oxiris®-AN69 membrane |
Primary outcome
Intensive care mortality
Time frame: During ICU care, 1 year
Intensive care mortality
90-day mortality
Time frame: Within 90 days from ICU admission, 90 days
90-day mortality
Days alive at day 90 without vasoactives, invasive mechanical ventilation and renal replacement therapy.
Time frame: 90 days following ICU admission, 90 days
Days alive at day 90 without vasoactives, invasive mechanical ventilation and renal replacement therapy.
6 secondary outcomes
Vasopressor support at 24 hours, 48 hours and 72 hours following CVVHDF initiation
Time frame: 24 hours, 48 hours and 72 hours following CVVHDF initiation
Fluid balance at 24 hours, 48 hours and 72 hours following CVVHDF initiation
Time frame: 24 hours, 48 hours and 72 hours following CVVHDF initiation
Cytokine levels at 24 hours, 48 hours and 72 hours following CVVHDF initiation
Time frame: 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
Time frame: 24 hours, 48 hours and 72 hours following CVVHDF initiation
Procalcitonin levels at 24 hours, 48 hours and 72 hours following CVVHDF initiation
Time frame: 24 hours, 48 hours and 72 hours following CVVHDF initiation
Renal recovery at 90-days following randomization
Time frame: 90 days following randomization, 90 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2021.
- Individual participant dataSharing planned: No
Related trials for Septic Shock
Active, not recruitingPhase 4
Thymosin Alpha 1 and IgM Levels in Sepsis
Sepsis, Septic Shock
Not yet recruiting
Vitamin C for Acute Kidney Injury in ACLF With Septic Shock: A Randomized Controlled Trial
Acute-on-Chronic Liver Failure (ACLF)
Not yet recruiting
ICU-SUCCEED for Survivors of Acute Respiratory Failure and Their Caregivers
Acute Respiratory Failure, Critical Illness
Not yet recruitingObservational study
Longitudinal Trajectories of Myocardial Work in Patients With Sepsis
Sepsis, Septic Shock Hyperdynamic
RecruitingObservational study
Immunothrombosis With Septic Shock Undergoing Renal Replacement Therapy With the OXIRIS Membrane
Sepsis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mikko J Järvisalo, MD, PhD principal investigator
Turku University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Combined HA380 hemoadsorption and continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes and Continuous veno-venous hemodiafiltration (CVVHDF) with Oxiris®-AN69 membranes in people with Septic Shock and Acute Kidney Injury, run by Turku University Hospital at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mikko J Järvisalo, MD, PhD (+35823130000, mikko.jarvisalo@tyks.fi), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intensive care mortality (time frame: During ICU care, 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2021.