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

• Sponsor: Mylan Specialty, LP (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00915681
• Collaborator: (none)
• Enrollment: 148
• Locations: 2
• Arm: 1
• Actual Duration (Months): 125
• Patients Per Site: 74
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Amatoxin Poisoning; Amanita Poisoning; Mushroom Poisoning; Liver Failure	Drug: Silibinin	Phase 2

Detailed Description

Patients with suspected amatoxin poisoning are reviewed for enrollment in the study by contacting the Legalon SIL study hotline [phone].

Study Design

• Study Type: Interventional
• Actual Enrollment: 148 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Nov 10, 2009
• Actual Primary Completion Date: Apr 10, 2020
• Actual Study Completion Date: Apr 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Legalon SIL Silibinin: loading dose of one hour infusion of 5 mg/kg, followed by 20 mg/kg/day infused continuously via pump	Drug: Silibinin; 20 mg/kg continuous IV is over 24 hours; Other Names: Legalon SIL

Outcome Measures

Primary Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Recruitment Hot Line for the United States	Somerset	New Jersey	United States	08873
2	Mylan Specialty LLP	Morgantown	West Virginia	United States	26504-4310

Sponsors and Collaborators

• Mylan Specialty, LP

Investigators

• Principal Investigator: Wallis Marsh, MD, WVU

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 3, 2018

More Information

Publications

None provided.

• Responsible Party: Mylan Specialty, LP
• ClinicalTrials.gov Identifier: NCT00915681
• Other Study ID Numbers: SB16A1.07
• First Posted: Jun 8, 2009
• Last Update Posted: Apr 7, 2022
• Last Verified: Jan 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Mylan Specialty, LP: amatoxin; amanita; mushroom poisoning; hepatic failure; milk thistle; Silibinin; Legalon
• Additional relevant MeSH terms: Liver Failure; Hepatic Insufficiency; Poisoning; Mushroom Poisoning; Silybin

Study Results

Participant Flow

Recruitment Details	148 screened, 102 treated FPI: 10-Nov-2009, LPO: 10-Apr-2020

Arm/Group Title	Legalon SIL
Arm/Group Description	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
Period Title: Overall Study
STARTED	148
COMPLETED	102
NOT COMPLETED	46

Baseline Characteristics

Arm/Group Title	Legalon SIL
Arm/Group Description	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
Overall Participants	102
Age (Count of Participants)
<=18 years	4 3.9%
Between 18 and 65 years	41 40.2%
>=65 years	26 25.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.9 (19.89)
Sex: Female, Male (Count of Participants)
Female	37 36.3%
Male	34 33.3%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United States	71 69.6%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Legalon SIL
Arm/Group Description	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
Measure Participants	0

Adverse Events

Time Frame	up to 10 days
Arm/Group Title	Legalon SIL
Arm/Group Description	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
All Cause Mortality
	Legalon SIL
	Affected / at Risk (%)	# Events
Total	0/102 (0%)
Serious Adverse Events
	Legalon SIL
	Affected / at Risk (%)	# Events
Total	0/102 (0%)
Other (Not Including Serious) Adverse Events
	Legalon SIL
	Affected / at Risk (%)	# Events
Total	0/102 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Mylan is allowed to require modifications.