Intravenous Milk Thistle (Silibinin-Legalon) for Hepatic Failure Induced by Amatoxin/Amanita Mushroom Poisoning

Study Overview
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Brief Summary
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Legalon® SIL will be administered to patients with amatoxin poisoning diagnosed by history, gastrointestinal symptoms, elevated liver enzymes, and/or diagnostic assay (should one become available). Patients may or may not also demonstrate abnormalities in bilirubin and/or creatinine. Treatment consists of a 5 mg/kg loading dose followed by 20 mg/kg/day via continuous infusion. The treating physician is expected to administer supportive therapy of his/her choosing but consistent with best practices. Legalon® SIL will be stopped when coagulopathy is no longer present, and when liver function tests have returned significantly towards the normal range. Patients will be followed 7-14 days after the end of Legalon® SIL therapy with follow up lab studies.

Detailed Description
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Patients with suspected amatoxin poisoning are reviewed for enrollment in the study by contacting the Legalon SIL study hotline (866) 520-4412.

Official Title
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A Phase II Multi-Center Open-Label Clinical Trial to Assess the Prevention of Liver Transplantation and/or Death Among Subjects Treated With Intravenous Silibinin (Legalon® SIL) for Amatoxin Induced Hepatic Failure

Conditions
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Amatoxin Poisoning, Amanita Poisoning, Mushroom Poisoning, Liver Failure

Intervention / Treatment
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* Drug: Silibinin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent(s) for clinical trial participation (due to the potential critical status of the subject upon presentation, consent may need to be obtained from Legally Authorized Representative (LAR) per sites consenting policy and ICH/GCP guidance) Signed Informed Consent for Clinical Trial participation History of eating foraged mushrooms Gastrointestinal symptoms suggestive of amatoxin poisoning (cramping abdominal pain, nausea, vomiting, and / or watery diarrhea) usually 24-48 hours after of mushroom ingestion Liver function tests suggestive of amatoxin poisoning: AST or ALT above the institutions upper limit of normal after mushroom ingestion Exclusion criteria: 1. Evidence of significant medical illness or any other abnormal laboratory finding that, in the Investigator's judgment, will substantially increase the risk associated with the subject's participation in, and completion of the study or could preclude the evaluation of the subject's response.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Legalon SIL<br>Silibinin: loading dose of one hour infusion of 5 mg/kg, followed by 20 mg/kg/day infused continuously via pump | Drug: Silibinin<br>* 20 mg/kg continuous IV is over 24 hours<br>* Other names: Legalon SIL;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Endpoint is the Percentage of Subjects Treated Under This Clinical Trial Without Morbidity (Liver Transplantation) and or Mortality (Death). | Study was terminated, no analysis performed as data are unavailable for most patients | not applicable as no analysis was performed | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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amatoxin, amanita, mushroom poisoning, hepatic failure, milk thistle, Silibinin, Legalon