Sepsis Clinical Trial
— OuTCAStOfficial title:
Observational Trial on Cytokine Adsorption in Sepsis
NCT number | NCT04306419 |
Other study ID # | 19-058 |
Secondary ID | |
Status | Recruiting |
Phase | |
First received | |
Last updated | |
Start date | November 15, 2020 |
Est. completion date | May 31, 2024 |
To determine the specific population of critically ill septic patients who benefit most from cytokine adsorption therapy with the HA-380 cartridge. Benefit of the treatment will be assessed on the basis of: - The scope of the effect of cytokine adsorption therapy in this specific population of critically ill patients expressed by cytokine variability within the patients - The scope of cytokine changes in passing the adsorption cartridge my measuring cytokine levels in the patient's blood directly before passing through the cartridge and directly after having passed through the cartridge. - The scope of changes in organ dysfunction expressed by SOFA scores that are repeatedly calculated during the treatment with cytokine adsorption and then daily until day 7 of the ICU treatment. - The scope of changes on cellular function on immune cells in serum samples taken before and after cytokine adsorption therapy. - The scope of removal of anti-infective drugs from the blood in passing through the cytokine adsorption cartridge by measuring antibiotic drug levels in the patients blood during the cytokine adsorption therapy - 30 day and 90 day mortality and location status in survivors
Status | Recruiting |
Enrollment | 100 |
Est. completion date | May 31, 2024 |
Est. primary completion date | June 28, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. >18 years of age 2. diagnosis of sepsis or septic shock with at least 2 organ-dysfunctions defined by SOFA score 3. baseline serum IL-6 > 1000 pg/ml, IL-10 levels >250 pg/ml or TNF-alpha levels > 100 ng/l. The baseline IL-6 measurement must be on the same calendar day that the cytokine adsorption is started, the baseline IL-10 or TNF-alpha can be taken up to 36h before because of higher turn-around times for these tests. 4. need for CRRT or ECMO therapy Exclusion Criteria: 1. Solid organ malignancies with or without treatment 2. Participation or enrollment in another clinical study within 30 day 3. Pregnant and lactating females If women of childbearing potential will be enrolled, a pregnancy test will be performed by assessing the value of ß-HCG in the routinely drawn blood and or urine. 4. Patient has been committed to an institution by legal or regulatory order 5. Participation in a parallel interventional clinical trial 6. The subject received an investigational drug within 30 days prior to inclusion into this project |
Country | Name | City | State |
---|---|---|---|
Germany | University Hospital RWTH Aachen | Aachen | NRW |
Lead Sponsor | Collaborator |
---|---|
RWTH Aachen University |
Germany,
Abraham E, Wunderink R, Silverman H, Perl TM, Nasraway S, Levy H, Bone R, Wenzel RP, Balk R, Allred R, et al. Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. A randomized, controlled, double-blind, multicenter clinical trial. TNF-alpha MAb Sepsis Study Group. JAMA. 1995 Mar 22-29;273(12):934-41. — View Citation
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Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb;41(2):580-637. doi: 10.1097/CCM.0b013e31827e83af. — View Citation
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Gruda MC, Ruggeberg KG, O'Sullivan P, Guliashvili T, Scheirer AR, Golobish TD, Capponi VJ, Chan PP. Broad adsorption of sepsis-related PAMP and DAMP molecules, mycotoxins, and cytokines from whole blood using CytoSorb® sorbent porous polymer beads. PLoS One. 2018 Jan 25;13(1):e0191676. doi: 10.1371/journal.pone.0191676. eCollection 2018. — View Citation
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Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA. 2010 Oct 27;304(16):1787-94. doi: 10.1001/jama.2010.1553. — View Citation
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* Note: There are 16 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Cytokine variability of Interleucin (IL) -6 , IL-8- IL-10, and Tumor Necrosis Factor-alpha (TNF-alpha) in the patient's IL-6 serum | as expressed by changes in concentration measured every two hours during a first cytokine adsorption treatment of eight hours and measured every four hours during a second eight hour cytokine adsorption treatment. The measurements will be set in relation to the baseline measurement taken immediately (<1 minute) immediately after the end of 8 hours of treatment with the HA 380 cartridge normalized to the initial baseline IL-6 serum concentration immediately before start of the treatment. The standard of care is a pause of four hours between the two treatments intervals | 16 hours | |
Secondary | Efficacy of relative cytokine removal from the patient's blood | by measuring relative differences for IL-6 , IL-8- IL-10 and TNF-alpha in blood samples taken directly before the blood enters the cartridge (inflow) and directly after passing the cartridge (outflow) during the treatments with the HA-380 cartrdige at the timepoints T2, T4, T6, T8 and T12, T16, T20. | 20 hours | |
Secondary | Vasopressor / lactate dose | Normalized change in vasopressor dose and lactate from baseline to after each 8 hours of treatment with the HA 380 cartridge | 8 hours | |
Secondary | P/F ratio | Normalized change in P/F ratio from baseline to after each 8 hours of treatment with the HA 380 cartridge | 8 hours | |
Secondary | Antibiotic drug levels | Changes in antibiotic drug levels between T0, T8 and T20 taken from the patient's blood samples at these time points. | 20 hours | |
Secondary | Sequential Organ Failure Assessment (SOFA) | Individual SOFA score changes and total SOFA Score changes over the course of each 8 hour treatment and the interval between the two treatments (T0,T2,T4,T6,T8,T12,T16,T20), and afterwards daily for a maximum of 7 days after the HA-380 treatment, until death of the patient or t until the patient leaves the ICU for, whichever occurs first.
breathing activity (minimum <100 mmHg gets 4 Points; maximum <400 gets 1 Points; higher Points means a worse outcome) Liver function (minimum 1,2 mg/dl of Bilirubin gets 1 Points; maximum >12 mg/dl Bilirubin gets 4 Points; higher Points means a worse outcome) Blood Coagulation (minimum <20 Thrombocyten x10^3/µl gets 4 Points; maximum >150 Thrombocyten x10^3/µl gets 4 Points; higher Points means a worse outcome) Renal function (minimum 1,2 mg/dl of Kreatinin gets 1 Points; maximum >5 mg/dl Kreatinin gets 4 Points; higher Points means a worse outcome) |
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