Clinical trial NCT06187220: Plasma Exchange for Amanita Toxin-induced Acute Liver Failure
Official title: Effect of Therapeutic Plasma Exchange on Liver Transplantation-free Survival in Amanita Toxin-induced Acute Liver Failure - a Multicenter Retrospective Study Over 10 Years
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Liver Failure
Keywords: Liver Failure
Amanita Toxin
Plasmapheresis
Liver Transplantation
Lead sponsor: Hannover Medical School
Sponsor class: OTHER
First posted: 2024-01-02
Enrollment: 111
Sex: ALL
Minimum age (years): 0
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients with Amanita toxin related acute liver failure, both adult and pediatric

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Liver Transplant free Survival
timeFrame: until day 28 from initial diagnosis of acute liver failure
Secondary outcomes:
measure: Overall Survival
timeFrame: until day 28 from initial diagnosis of acute liver failure
measure: Liver transplantation
timeFrame: until day 28 from initial diagnosis of acute liver failure
measure: High urgency (HU) listing for liver transplantation
timeFrame: until day 28 from initial diagnosis of acute liver failure
measure: Acute kidney injury (AKI) and max. grade of AKI (I-III)
timeFrame: until day 28 from initial diagnosis of acute liver failure
measure: Renal Replacement Therapy (RRT)
timeFrame: until day 28 from initial diagnosis of acute liver failure (encephalopathy of any grade and coagulopathy with INR > 1.5)
measure: Vasopressor therapy
timeFrame: until day 28 from initial diagnosis of acute liver failure (encephalopathy of any grade and coagulopathy with INR > 1.5)
measure: Invasive ventilation
timeFrame: until day 28 from initial diagnosis of acute liver failure (encephalopathy of any grade and coagulopathy with INR > 1.5)
measure: Maximum grade of hepatic encephalopathy (HE)
timeFrame: until day 28 from initial diagnosis of acute liver failure (encephalopathy of any grade and coagulopathy with INR > 1.5)
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: University Hospital Aachen (RWTH)
city: Hannover
country: Germany
facility: Hannover Medical School
city: Bergamo
country: Italy
facility: ASST Ospedale Papa Giovanni XXIII
city: Mexico City
country: Mexico
facility: INCMNSZ
city: Lisbon
country: Portugal
facility: Curry Cabral Hospital
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
Study officials:
affiliation: Hannover Medical School, Hannover Germany
name: Klaus Stahl, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hannover Medical School, Hannover Germany
name: Richard Taubert, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.