CytoSorb® in Patients With Acute on Chronic Liver Failure (HepOnFire)

A Prospective, Multi-Centre, Propensity Score Based Matched Pair Controlled, Study of Standard Medical Care Plus CytoSorb® 300 mL Device Compared to Standard Medical Care Alone in Patients With Acute on Chronic Liver Failure Due to Severe Alcoholic Hepatitis in Combination With Systemic Hyperinflammation and Acute on Chronic Liver Failure Score ≥2

The objective of this study is to assess the safety and performance of the CytoSorb® therapy in patients with Acute on Chronic Liver Failure (ACLF) grade ≥ 2 due to a severe alcohol induced hepatitis (Maddrey DF > 32) and a severe inflammatory response.

Study Overview

• Status: Withdrawn
• Conditions: Alcoholic Hepatitis; Acute on Chronic Liver Failure
• Intervention / Treatment: Device: CytoSorb® treatment

• Study Type: Observational

Contacts and Locations

Study Locations

• Germany
  • Bochum, Germany, 44892
    • Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH
  • Rostock, Germany, 18055
    • University of Rostock

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

30 patients meeting the eligibility requirements of the study will receive Standard of Care treatment for alcoholic hepatitis (including steroid therapy according to AASLD/EASL guidelines and extracorporeal treatments when indicated) plus treatment with the CytoSorb® 300 mL device, a hemoperfusion adsorbent CE-certified therapy for the removal of bilirubin and pro-inflammatory cytokines (CytoSorb group).

30 propensity score matched controls from a patient database will be drawn from existing US and European sources (prospectively collected databases from geographies with comparable Standard of Care). The 30 CytoSorb group patients will be compared with these database patients.

Description

Inclusion Criteria:

1. Age≥18
2. Signed Informed Consent Form (ICF)
3. Total bilirubin ≥ 8 mg/dL

4. Acute Alcoholic Hepatitis diagnosed by EtOH consumption within 6 weeks of onset of symptoms, exclusion of other causes for jaundice and liver biopsy or at least 2 out of the following symptoms:

   • Hepatomegaly
   • AST > ALT
   • Elevated WBC
   • Ascites
5. Maddrey DF > 32

6. Systemic inflammation as defined by 2 fulfilled criteria out of:

   • leucocytosis
   • body temperature > 38°C
   • tachycardia > 90 bpm
   • tachypnoeia > 20 breaths/min
7. ACLF grade ≥2
8. Creatinine >2 mg/dl and increase >1.5 mg/dl despite standard of care

Exclusion Criteria:

1. Platelets < 40,000/mm3
2. INR > 3.5
3. MELD Score > 35
4. AST > 500 IU/l
5. Bilirubin reduction > 20% in prior 72 hours (early responders to conventional Standard of Care (SOC))
6. Uncontrolled infection, bleeding or hemodynamic instability
7. Small liver size (diagnosed by imaging, ultrasound/CT)
8. Chronic dialysis
9. Contraindications for CytoSorb® according to Instructions for Use
10. ACLF grade <2

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

CytoSorb group

Device: CytoSorb® treatment; Patients with Acute on Chronic Liver Failure (ACLF) due to Severe Alcoholic Hepatitis in combination with systemic inflammation and ACLF grade ≥2 will be enrolled in this study. Every patient that is screened, fulfills the inclusion/exclusion criteria, and consents to the study, will be allowed to enter the study. Patients will receive Standard of Care treatment for alcoholic hepatitis plus treatment with the CytoSorb® 300 mL device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients in each group with Acute on Chronic Liver Failure (ACLF) grade <2	To evaluate effectiveness of the CytoSorb® treatment compared to control group by comparing the proportion of patients in each group with ACLF grade <2 at the end of Day 7 after CytoSorb® therapy start (assessed by https://www.efclif.com/scientific-activity/score-calculators/clif-c-aclf).	7 Days
Safety of CytoSorb treatment	To evaluate if CytoSorb® treatment plus Standard Medical Care (SMC) compared to SMC alone is safe and tolerable as assessed by the incidence of SA(D)Es, ADEs, DDs, SADEs, and USADEs. SAE - Severe Adverse Effect; ADE - Adverse Device Effect; SADE - Severe Adverse Device Effect; DD - Device Deficiencies; USADE - Unexpected Serious Adverse Device Effect	30 Days

Collaborators and Investigators

• Sponsor: CytoSorbents Europe GmbH

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2022
• Primary Completion (Anticipated): March 1, 2023
• Study Completion (Anticipated): April 1, 2023

Study Registration Dates

• First Submitted: November 12, 2021
• First Submitted That Met QC Criteria: November 12, 2021
• First Posted (Actual): November 23, 2021

Study Record Updates

• Last Update Posted (Actual): November 29, 2022
• Last Update Submitted That Met QC Criteria: November 23, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Alcohol-Related Disorders; Substance-Related Disorders; Liver Diseases; Liver Failure, Acute; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; End Stage Liver Disease; Liver Failure; Hepatic Insufficiency; Acute-On-Chronic Liver Failure; Hepatitis; Hepatitis, Alcoholic
• Other Study ID Numbers: L02HOF

Drug and device information, study documents

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