Pancreatitis CytoSorbents (CytoSorb®) Inflammatory Cytokine Removal

Study Overview
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Brief Summary
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Severe acute pancreatitis (SAP) has a mortality of up to 42%. The outcome of SAP is related to the development of SIRS and consecutive organ failures. Due to the lack of a causative therapy except the removal of bile duct stones, therapy is predominantly symptomatic. With regard to a marked inflammatory response (cytokine storm) during the early phase of SAP extracorporeal cytokine removal is a promising therapeutic approach. This prospective case control study investigates the impact of early extracorporeal cytokine adsorption with the CytoSorb®-device on haemodynamics (primary endpoint) and several secondary outcomes.

Detailed Description
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Severe acute pancreatitis (SAP) has a mortality of up to 42%. The outcome of SAP is related to the development of SIRS and consecutive organ failures. Due to the lack of a causative therapy except the removal of bile duct stones, therapy is predominantly symptomatic. Severity and mortality are associated to an early systemic inflammatory response syndrome (SIRS) and to septic complications at a later stage of disease. With regard to a marked inflammatory response (cytokine storm) during the early phase of SAP extracorporeal cytokine removal is a promising therapeutic approach. This prospective case control study investigates the impact of early extracorporeal cytokine adsorption with the CytoSorb® device on haemodynamics (primary endpoint) and several secondary outcomes. Patients with high probability of SAP (APACHE-II-score ≥10) are eligible for 7 days after the onset of pain. The patients will be treated for 48h with two consecutive 24h sessions of cytokine absorption with the CytoSorb®-device. All patients will be under haemodynamic Monitoring with transpulmonary thermodilution The primary endpoint is defined as an improvement of the vasopressor dependency index of ≥20% (if no vasoactive drugs are used at baseline, the cardiac power index cardiac power index (CPI) will be used as primary endpoint). The outcome analysis will be based on comparison of the incidence of the primary endpoint in 30 Intervention patients compared to 60 matched controls.

Official Title
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Pancreatitis CytoSorbents (CytoSorb®) Inflammatory Cytokine Removal: A Prospective Study.

Conditions
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Pancreatitis, Acute, SIRS

Intervention / Treatment
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* Device: CytoSorb


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Proven acute pancreatitis: typical pain at least 3-fold increase in serum lipase onset of pain within 7 days before inclusion AND APACHE-II ≥10 AND ≥1 criterion of severe sepsis AND Haemodynamic monitoring with transpulmonary thermodilution AND ≥ 1 marker of poor prognosis of acute pancreatitis: Haematocrit > 44% (men), >40% (women) Blood glucose > 125 mg/dL C-reactive protein (CRP) > 10mg/dL Computed tomography score category C-E Age >55 years Leukocytes >16 G/L Glutamate oxaloacetate transferase (GOT) >250 U/L Lactate dehydrogenase (LDH) >350 U/L Calcium <2,0mmol/L Exclusion Criteria: pregnancy lack of informed consent of patient or representative pre-existing disease with life expectancy <3 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Inflammatory cytokine removal by Cyto Sorb treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CytoSorb<br>CytoSorb therapy for 48h | Device: CytoSorb<br>* Two consecutive 24h treatments with the CytoSorb-device<br>|
| No Intervention: Matched controls<br>60 matched controls with SAP and transpulmonary thermodilution monitoring | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemodynamics | Improvement of the vasopressor dependency index >=20%. (Improvement of cardiac power index >=20% in case of no vasopressor use at baseline) | Within 48h after the onset of CytoSorb treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality-1 | 28-days-mortality | 28 days from inclusion into the study | 
| Mortality-2 | ICU-mortality | From admission to the ICU until discharge or transfer from the ICU (up to one year) | 
| Mortality-3 | Hospital-mortality | From admission to discharge from the hospital (up to one year) | 
| Inflammation | IL-6, CRP and PCT-values levels compared to before CytoSorb treatment | Within 48h after the onset of CytoSorb treatment | 
| Respiratory outcome | Ventilator-free days | Within 28 days after the onset of CytoSorb treatment | 
| Renal function and its Change over time | Daily classification according to KDIGO; comparison vs. before Cyto Sorb treatment | Within 28 days after the onset of CytoSorb treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe acute pancreatitis, Haemodynamic monitoring, Cytokine removal, Vasopressor dependency index