Pancreatitis CytoSorbents (CytoSorb®) Inflammatory Cytokine Removal (PACIFIC)

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

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.

Study Overview

• Status: Unknown
• Conditions: SIRS; Pancreatitis, Acute
• Intervention / Treatment: Device: CytoSorb

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: CytoSorb; CytoSorb therapy for 48h	Device: CytoSorb; Two consecutive 24h treatments with the CytoSorb-device
NO_INTERVENTION: Matched controls; 60 matched controls with SAP and transpulmonary thermodilution monitoring

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Technical University of Munich
• Collaborators: CytoSorbents Europe GmbH
• Investigators: Principal Investigator: Wolfgang Huber, Professor, II. Medizinische Klinik; Klinikum rechts der Isar; Technische Universität München

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): March 15, 2017
• Primary Completion (ANTICIPATED): February 1, 2018
• Study Completion (ANTICIPATED): July 1, 2018

Study Registration Dates

• First Submitted: January 13, 2017
• First Submitted That Met QC Criteria: March 10, 2017
• First Posted (ACTUAL): March 17, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 17, 2017
• Last Update Submitted That Met QC Criteria: March 10, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Severe acute pancreatitis; Haemodynamic monitoring; Cytokine removal; Vasopressor dependency index
• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis
• Other Study ID Numbers: PACIFIC 10-2015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No