Plasma Exchange for Amanita Toxin-induced Acute Liver Failure (Amanita-Pex)

Effect of Therapeutic Plasma Exchange on Liver Transplantation-free Survival in Amanita Toxin-induced Acute Liver Failure - a Multicenter Retrospective Study Over 10 Years

Retrospective evaluation of the value of additive therapeutic plasma exchange (PEX) compared to standard medical therapy (SMT) in Amanita toxin-associated acute liver failure in children and adolescents within the last 10 years at a international group of liver transplant centers.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Liver Failure
• Intervention / Treatment: Device: Therapeutic Plasma Exchange (PEX)

Detailed Description

Amanita toxin-associated acute liver failure is a life-threatening condition that can often lead to the need for an emergency liver transplantation. The disease may also be fatal, particularly in patients who are not eligible for a liver transplant due to advanced age or corresponding comorbidities.

Therapeutic plasma exchange treatment has been shown to significantly improve patient survival in other cases of acute liver failure and has since become standard treatment for acute liver failure in many, but not all, liver transplant centers. However, no patients with Amanita toxin-associated acute liver failure were included in these cohorts.

The hypothesis of the planned study is that an additive therapeutic plasma exchange treatment (PEX) can improve liver transplantation-free survival in these patients compared to standard medical therapy (SMT) alone. Since the therapy procedure in different transplant centers in differs with regard to the use of therapeutic plasma exchange, we are therefore planning a multicenter retrospective comparison of PEX with SMT with regard to transplant-free survival and other clinical endpoints. For this very small cohort of patients with acute liver failure, which also varies in frequency depending on the season and weather conditions, there will certainly never be a sufficiently powered randomized and controlled study. This analysis may change the standard procedure for patients with Amanita toxin-associated acute liver failure.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Klaus Stahl, MD; Phone Number: 0049-15172405294; Email: stahl.klaus@mh-hannover.de
• Study Contact Backup: Name: Richard Taubert, MD; Email: taubert.richard@mh-hannover.de

Study Locations

• Germany
  • Aachen, Germany
    • University Hospital Aachen (RWTH)
    • Contact: Karsten Große, MD; Email: kargrosse@ukaachen.de
  • Hannover, Germany
    • Hannover Medical School
    • Contact: Bahar Nalbant, MD; Email: nalbant.bahar@mh-hannover.de
    • Principal Investigator: Richard Taubert, MD
    • Principal Investigator: Klaus Stahl, MD
• Italy
  • Bergamo, Italy
    • ASST Ospedale Papa Giovanni XXIII
    • Contact: Angelo Di Giorgio, MD; Email: adigiorgio@asst-pg23.it
• Mexico
  • Mexico City, Mexico
    • INCMNSZ
    • Contact: Ricardo Macías-Rodríguez, MD
    • Contact: Email: ricardo.maciasr@incmnsz.mx
• Portugal
  • Lisbon, Portugal
    • Curry Cabral Hospital
    • Contact: Filipe Sousa Cardoso, MD; Email: filipe_sousacardoso@hotmail.com
• Spain
  • Barcelona, Spain
    • Hospital Clínic de Barcelona
    • Contact: N. David Toapanta-Gaibor, MD; Email: toapanta@clinic.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients with Amanita toxin related acute liver failure, both adult and pediatric

Description

Inclusion Criteria:

• Acute liver failure (presence of hepatic encephalopathy of grade I or higher and a coagulopathy with an INR > 1.5)
• Amanita Toxin related acute liver failure

Exclusion Criteria:

• Acute liver failure of other reason than Amanita Toxin
• Amanita Toxin associated Hepatitis or severe hepatitis without fulfilling the criteria of acute liver failure

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Therapeutic Plasma Exchange (PEX); Patients receiving in addition to Standard Medical Therapy (SMT) at least one treatment with Therapeutic Plasma Exchange (PEX)	Device: Therapeutic Plasma Exchange (PEX); Therapeutic plasma exchange with treatment sessions >=1 replacing varying fractions of patient´s whole plasma with healthy donor plasma
Standard Medical Therapy (SMT); Patients receiving only Standard Medical Therapy (SMT) of Amanita Toxin associated acute liver failure, including intensive care support (invasive ventilation, vasopressors, renal replacement therapy), silibinin and n-acetylcystein. Included in this group are also patients receiving albumine dialysis or other extracorporeal liver assist therapies excluding therapeutic plasma exchange.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver Transplant free Survival	Survival and free of liver transplantation until day 28 from initial diagnosis of acute liver failure (encephalopathy of any grade and coagulopathy with INR > 1.5)	until day 28 from initial diagnosis of acute liver failure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Survival until day 28 from initial diagnosis of acute liver failure (encephalopathy of any grade and coagulopathy with International normalized ratio (INR) > 1.5)	until day 28 from initial diagnosis of acute liver failure
Liver transplantation	Liver transplantation until day 28 from initial diagnosis of acute liver failure (encephalopathy of any grade and coagulopathy with INR > 1.5)	until day 28 from initial diagnosis of acute liver failure
High urgency (HU) listing for liver transplantation	Initiated high urgency listing for liver transplantation until day 28 from initial diagnosis of acute liver failure (encephalopathy of any grade and coagulopathy with INR > 1.5)	until day 28 from initial diagnosis of acute liver failure
Acute kidney injury (AKI) and max. grade of AKI (I-III)	Acute kidney injury and max. grade of AKI (I-III) until day 28 from initial diagnosis of acute liver failure (encephalopathy of any grade and coagulopathy with INR > 1.5)	until day 28 from initial diagnosis of acute liver failure
Renal Replacement Therapy (RRT)	Initiated renal replacement therapy until day 28 from initial diagnosis of acute liver failure (encephalopathy of any grade and coagulopathy with INR > 1.5)	until day 28 from initial diagnosis of acute liver failure (encephalopathy of any grade and coagulopathy with INR > 1.5)
Vasopressor therapy	Initiated vasopressor therapy until day 28 from initial diagnosis of acute liver failure (encephalopathy of any grade and coagulopathy with INR > 1.5)	until day 28 from initial diagnosis of acute liver failure (encephalopathy of any grade and coagulopathy with INR > 1.5)
Invasive ventilation	Initiated invasive ventilation until day 28 from initial diagnosis of acute liver failure (encephalopathy of any grade and coagulopathy with INR > 1.5)	until day 28 from initial diagnosis of acute liver failure (encephalopathy of any grade and coagulopathy with INR > 1.5)
Maximum grade of hepatic encephalopathy (HE)	Maximum grade of hepatic encephalopathy (HE) until day 28 from initial diagnosis of acute liver failure (encephalopathy of any grade and coagulopathy with INR > 1.5)	until day 28 from initial diagnosis of acute liver failure (encephalopathy of any grade and coagulopathy with INR > 1.5)

Collaborators and Investigators

• Sponsor: Hannover Medical School
• Investigators: Principal Investigator: Klaus Stahl, MD, Hannover Medical School, Hannover Germany; Principal Investigator: Richard Taubert, MD, Hannover Medical School, Hannover Germany

Publications and helpful links

General Publications

• Stahl K, Hadem J, Schneider A, Manns MP, Wiesner O, Schmidt BMW, Hoeper MM, Busch M, David S. Therapeutic plasma exchange in acute liver failure. J Clin Apher. 2019 Oct;34(5):589-597. doi: 10.1002/jca.21737. Epub 2019 Jul 26.
• Stahl K, Bode C, David S. Bridging patients with acute-on-chronic liver failure for transplantation: plasma exchange to stabilize multiorgan failure? Intensive Care Med. 2023 Jul;49(7):890-891. doi: 10.1007/s00134-023-07092-x. Epub 2023 May 13. No abstract available.
• Stahl K, Busch M, Fuge J, Schneider A, Manns MP, Seeliger B, Schmidt JJ, Wiesner O, Schmidt BMW, Taubert R, Vondran FWR, Hoeper MM, David S. Therapeutic plasma exchange in acute on chronic liver failure. J Clin Apher. 2020 Aug;35(4):316-327. doi: 10.1002/jca.21799. Epub 2020 Jun 24.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: December 16, 2023
• First Submitted That Met QC Criteria: December 29, 2023
• First Posted (Actual): January 2, 2024

Study Record Updates

• Last Update Posted (Estimated): January 3, 2024
• Last Update Submitted That Met QC Criteria: December 30, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Plasmapheresis; Liver Transplantation; Liver Failure; Amanita Toxin
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency; Liver Failure, Acute
• Other Study ID Numbers: Amanita-Pex

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Plan to share on reasonable request

Drug and device information, study documents

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