Clinical trial NCT03082469: Pancreatitis CytoSorbents (CytoSorb®) Inflammatory Cytokine Removal
Official title: Pancreatitis CytoSorbents (CytoSorb®) Inflammatory Cytokine Removal: A Prospective Study.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Pancreatitis, Acute
SIRS
Keywords: Severe acute pancreatitis
Haemodynamic monitoring
Cytokine removal
Vasopressor dependency index
Lead sponsor: Technical University of Munich
Sponsor class: OTHER
Collaborators: name: CytoSorbents Europe GmbH
First posted: 2017-03-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Inflammatory cytokine removal by Cyto Sorb treatment
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Haemodynamics
timeFrame: Within 48h after the onset of CytoSorb treatment
Secondary outcomes:
measure: Mortality-1
timeFrame: 28 days from inclusion into the study
measure: Mortality-2
timeFrame: From admission to the ICU until discharge or transfer from the ICU (up to one year)
measure: Mortality-3
timeFrame: From admission to discharge from the hospital (up to one year)
measure: Inflammation
timeFrame: Within 48h after the onset of CytoSorb treatment
measure: Respiratory outcome
timeFrame: Within 28 days after the onset of CytoSorb treatment
measure: Renal function and its Change over time
timeFrame: Within 28 days after the onset of CytoSorb treatment
Other outcomes:
Locations:
Study officials:
affiliation: II. Medizinische Klinik; Klinikum rechts der Isar; Technische Universität München
name: Wolfgang Huber, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Huber W, Algul H, Lahmer T, Mayr U, Lehmann M, Schmid RM, Faltlhauser A. Pancreatitis cytosorbents (CytoSorb) inflammatory cytokine removal: A Prospective Study (PACIFIC). Medicine (Baltimore). 2019 Jan;98(4):e13044. doi: 10.1097/MD.0000000000013044.