Amatoxin Poisoning, Amanita Poisoning, Mushroom Poisoning, Liver Failure
Conditions
Keywords
amatoxin, amanita, mushroom poisoning, hepatic failure, milk thistle, Silibinin, Legalon
Brief summary
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
Patients with suspected amatoxin poisoning are reviewed for enrollment in the study by contacting the Legalon SIL study hotline (866) 520-4412.
Interventions
DRUGSilibinin
20 mg/kg continuous IV is over 24 hours
Sponsors
Mylan Specialty, LP
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. 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 2. History of eating foraged mushrooms 3. Gastrointestinal symptoms suggestive of amatoxin poisoning (cramping abdominal pain, nausea, vomiting, and / or watery diarrhea) usually 24-48 hours after of mushroom ingestion 4. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Endpoint is the Percentage of Subjects Treated Under This Clinical Trial Without Morbidity (Liver Transplantation) and or Mortality (Death). | not applicable as no analysis was performed | Study was terminated, no analysis performed as data are unavailable for most patients |
Countries
United States
Participant flow
Recruitment details
148 screened, 102 treated FPI: 10-Nov-2009, LPO: 10-Apr-2020
Participants by arm
| Arm | Count |
|---|---|
| Legalon SIL Silibinin: loading dose of one hour infusion of 5 mg/kg, followed by 20 mg/kg/day infused continuously via pump
Silibinin: 20 mg/kg/day IV | 102 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Screening failures | 46 |
Baseline characteristics
| Characteristic | Legalon SIL | — |
|---|---|---|
| Age, Categorical <=18 years | 4 Participants | — |
| Age, Categorical >=65 years | 26 Participants | — |
| Age, Categorical Between 18 and 65 years | 41 Participants | — |
| Age, Continuous | 54.9 years STANDARD_DEVIATION 19.89 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 71 participants | — |
| Sex: Female, Male Female | 37 Participants | — |
| Sex: Female, Male Male | 34 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 102 |
| other Total, other adverse events | 0 / 102 |
| serious Total, serious adverse events | 0 / 102 |
Outcome results
Primary
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
Time frame: not applicable as no analysis was performed
Population: The data is determined to be unreliable and this has been communicated to FDA and the IRB/EC; Therefore the study data cannot be analyzed and summarized to be reported except for the basic information.