Extracorporal Cytokin Removal in Septic Shock: a Prospective, Randomized, Multicenter Clinical Trial
NCT ID: NCT04742764
Last Updated: 2023-04-20
Study Results
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Basic Information
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SUSPENDED
PHASE3
135 participants
INTERVENTIONAL
2024-01-01
2027-10-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
SINGLE
Study Groups
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Group A
Patients randomized to standard medical therapy.
Standard medical therapy
Standard medical therapy (according to the Surviving Sepsis Campaign) will include standard monitoring (pulseoximetry, 5-lead ECG, continuous invasive blood pressure monitoring, central venous cannulation and 24 with PiCCO-technology. Norepinephrine as a vasopressor and dobutamine - if needed - as an inotrope will be administered by the attending physician.
Group B
Patients randomized to cytokine removal therapy with Cytosorb, with the adsorber device changed in every 12 hours.
Standard medical therapy plus cytokine removal treatment using Cytosorb, with the adsorber changed in every 12 hours
Standard medical therapy, as discussed above will be applied. Furthermore, Cytosorb will be administered as soon as it is possible after randomization but not later than 2 hour (start of the treatment, T0). In a blood pump circuit in pre-haemofilter position, using a kidney replacement device of Fresenius Multifiltrate as a solo therapy or in combination with renal replacement therapy. It will be run in CVVHD, CVVHDF or CVVH mode with a 150 and 200 ml/min blood flow. Anticoagulation will be applied intravenously with heparin, low molecular weight heparin or citrate. The aim of the pump flow rate will be 100-400 mL/min, and the flow rate will be recorded. Possible shock reversal will be assessed by the physician attending. Adsorber cartridges will be changed in every 12 hours. End of the study period (Te): 12 hours after shock reversal, death of the patient, or maximum of five days, whichever happens first.
Group C
Patients randomized to cytokine removal therapy with Cytosorb, with the adsorber device changed in every 24 hours.
Standard medical therapy plus cytokine removal treatment using Cytosorb, with the adsorber changed in every 24 hours
The standard medical therapy and method of Cytosorb treatment as detailed above will be applied. Adsorber cartridges will be changed in every 24 hours.
Interventions
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Standard medical therapy
Standard medical therapy (according to the Surviving Sepsis Campaign) will include standard monitoring (pulseoximetry, 5-lead ECG, continuous invasive blood pressure monitoring, central venous cannulation and 24 with PiCCO-technology. Norepinephrine as a vasopressor and dobutamine - if needed - as an inotrope will be administered by the attending physician.
Standard medical therapy plus cytokine removal treatment using Cytosorb, with the adsorber changed in every 12 hours
Standard medical therapy, as discussed above will be applied. Furthermore, Cytosorb will be administered as soon as it is possible after randomization but not later than 2 hour (start of the treatment, T0). In a blood pump circuit in pre-haemofilter position, using a kidney replacement device of Fresenius Multifiltrate as a solo therapy or in combination with renal replacement therapy. It will be run in CVVHD, CVVHDF or CVVH mode with a 150 and 200 ml/min blood flow. Anticoagulation will be applied intravenously with heparin, low molecular weight heparin or citrate. The aim of the pump flow rate will be 100-400 mL/min, and the flow rate will be recorded. Possible shock reversal will be assessed by the physician attending. Adsorber cartridges will be changed in every 12 hours. End of the study period (Te): 12 hours after shock reversal, death of the patient, or maximum of five days, whichever happens first.
Standard medical therapy plus cytokine removal treatment using Cytosorb, with the adsorber changed in every 24 hours
The standard medical therapy and method of Cytosorb treatment as detailed above will be applied. Adsorber cartridges will be changed in every 24 hours.
Eligibility Criteria
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Inclusion Criteria
* Septic shock both medical or surgical ethiology (except for re-operation)
* APACHE \> 25
* Mechanical ventilation
* Norepinephrine requirement ≥0.4 µg/kg/min for at least 30 minutes, when hypovolemia is highly unlikely as indicated by invasive hemodynamic measurements assessed by the attending physician
* Invasive hemodynamic monitoring to determine cardiac output and derived variables
* Procalcitonin level ≥ 10 ng/ml
* Inclusion within 6 - 24 hours after the onset of vasopressor need and after all standard therapeutic measures have been implemented without clinical improvement (i.e.: the shock is considered refractory)
Exclusion Criteria
* Lack of health insurance
* Pregnancy
* Standard guideline-based medical treatment not exhausted (detailed below at 3.6) standard medical therapy)
* End stage organ failure
* New York Heart Association Class IV.
* Chronic renal failure with eGFR \< 15 ml/min/1,73 m2
* End-stage liver disease (MELD score \>30, Child-Pugh score Class C
* Unlikely survival for 24 hours according to the attending physician
* Acute onset of hemato-oncological illness
* Post cardiopulmonary resuscitation care
* Re-operation in context with the septic insult
* Immunosuppression
* systemic steroid therapy (\>10 mg prednisolon/day)
* immunosuppressive agents (i.e.: methotrexate, azathioprine, cyclosporin, tacrolimus, cyclophosphamide)
* Human immunodeficiency virus infection (active AIDS): HIV-VL \> 50 copies/mL
* Patients with transplanted vital organs
* Thrombocytopenia (\<20.000/ml)
* More than 10%-of body surface area with a third-degree burn
* Acute coronary syndrome
18 Years
80 Years
ALL
No
Sponsors
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University of Pecs
OTHER
Responsible Party
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Principal Investigators
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Péter Hegyi, MD, PhD, DSc
Role: PRINCIPAL_INVESTIGATOR
Insitute for Translational Medicine, University of Pécs, Medical School, Pécs, Hungary
Locations
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Institute for Translational Medicine, University of Pécs
Pécs, , Hungary
Countries
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References
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Other Identifiers
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OGYÉI/65049/2020
Identifier Type: -
Identifier Source: org_study_id
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