Pancreatitis CytoSorbents (CytoSorb®) Inflammatory Cytokine Removal

Phase 4

• Conditions: Pancreatitis, Acute; SIRS
• Interventions: Device: CytoSorb

• Registration Number: NCT03082469
• Lead Sponsor: Technical University of Munich

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.

Study Timeline

• Study First Submitted: 2017-01-13
• Status Verified: 2017-03
• Study First Submitted QC: 2017-03-10
• Last Update Submitted: 2017-03-10
• Study Start: 2017-03-15
• Study First Posted: 2017-03-17
• Last Update Posted: 2017-03-17
• Primary Completion: 2018-02
• Study Completion: 2018-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CytoSorb	CytoSorb	CytoSorb therapy for 48h

Primary Outcome Measures

Name	Time	Method
Haemodynamics	Within 48h after the onset of CytoSorb treatment	Improvement of the vasopressor dependency index \>=20%. (Improvement of cardiac power index \>=20% in case of no vasopressor use at baseline)

Secondary Outcome Measures

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