Clinical trial

Dosing of Extracorporeal Cytokine Removal In Septic Shock (DECRISS): a Prospective, Randomized, Multicenter Clinical Trial

Name

OGYÉI/65049/2020

Description

Sepsis and septic shock have mortality rates between 20-50%. When standard therapeutic measures fail to improve patients' condition, additional therapeutic alternatives are applied to reduce morbidity and mortality. One of the most recent alternatives is extracorporeal cytokine hemoadsorption. One of the most tested devices is CytoSorb, however, there are a lot of open questions, such timing, dosing and of course its overall efficacy. This study aims to compare the efficacy of standard medical therapy (Group A, SMT) and continuous extracorporeal cytokine removal with CytoSorb therapy in patients with early refractory septic shock. Furthermore, we compare the dosing of CytoSorb adsorber device - as the cartridge will be changed in every (12 Group B) or 24 hours (Group C).

Trial arms

Trial start

2024-01-01

Estimated PCD

2026-10-31

Trial end

2027-10-31

Phase

Early phase I

Treatment

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.

Arms:

Group A

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.

Arms:

Group B

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.

Arms:

Group C

Size

135

Primary endpoint

Shock reversal

At the time of shock reversal assessed up to 5 days

Time to shock reversal

From the start of the treatment until shock reversal assessed up to 5 days

Eligibility criteria

Inclusion Criteria: * Septic shock as defined by the Sepsis-3 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: * Patients under 18 years and over 80 * 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

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Prospective, randomized, controlled, three-arm, open-label, international, multi-centre, phase III study', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'SINGLE', 'maskingDescription': 'No masking is applied in this study, as it is impossible to blind the medical personnel and participants. Statisticians will be blinded to allocation', 'whoMasked': ['OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 135, 'type': 'ESTIMATED'}}

Updated at

2023-04-20

1 organization

1 product

1 indication

Organization

University of Pecs

Product

Standard medical therapy

Indication

Septic shock