Recommendation for Use of the Extract of Milk Thistle (Containing Silymarin) in Patients Receiving Anti-Tuberculosis Drugs to Reduce the Risk of Hepatotoxicity, If Positive Results Were Observed
This study was performed in Al-Zahra hospital affiliated to Isfahan University of Medical Sciences. Patients who had inclusion criteria were randomly assigned to two groups of drugs and control. All patients received standard anti-TB regimen according to the national protocol. The patients of drug used liver support capsule, twice daily for 2 weeks, while patients in the control group received the standard anti-TB drugs alone. All patients were measured and recorded ALT, AST, ALP and serum bilirubin at the beginning of the study and before the start of interventions and then weekly for up to 2 weeks.
Participants/Inclusion and exclusion criteria
Age ≥ 18 years old; pulmonary or outer pulmonary tuberculosis; taking first line of anti-TB drugs (Isoniazid, Rifampin and Pyrazinamide); don’t take first line of anti-TB drugs for the last 8 weeks; don’t use of known hepatotoxic drugs (e.g., sodium valproate, methotrexate, sulfonamides); not taking acetaminophen persistently; not using systemic glucocorticoids simultaneously; don’t use supplements containing Silymarin in the last 4 weeks; not using alcohol; not use antioxidants (such as vitamins E,C); lack of chronic liver or kidney disease; and non pregnant; non lactating women.
Intervention groups
Drug group: taking capsule of dry extract of Milk Thistle Seed (Liver Support) Containing 150 mg of Silymarin, twice daily from the Onset of Anti-Tuberculosis Drugs Control group: taking Anti-Tuberculosis drugs alone
Main outcome variables
Serum Levels of Liver Enzymes (ALT, AST, ALP) and Total and Direct Bilirubin; The Number of Cases of Acute Liver Injury
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20150721023282N9
Registration date:2020-03-30, 1399/01/11
Registration timing:retrospective
Last update:2020-03-30, 1399/01/11
Update count:0
Registration date
2020-03-30, 1399/01/11
Registrant information
Name
Rasool Soltani
Name of organization / entity
Isfahan University of Medical Sciences
Country
Iran (Islamic Republic of)
Phone
+98 31 3792 7067
Email address
soltani@pharm.mui.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2017-03-21, 1396/01/01
Expected recruitment end date
2018-08-22, 1397/05/31
Actual recruitment start date
2017-03-21, 1396/01/01
Actual recruitment end date
2018-08-22, 1397/05/31
Trial completion date
2018-09-22, 1397/06/31
Scientific title
Evaluation of the effect of Milk Thistle in the prevention of anti-tuberculosis drugs-induced hepatotoxicity: A randomized controlled clinical trial
Public title
Evaluation of the effect of Milk Thistle in the prevention of anti-tuberculosis drugs-induced hepatotoxicity: A randomized controlled clinical trial
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Age ≥ 18 years
Pulmonary or outer pulmonary tuberculosis
Taking first line of anti-TB drugs (Isoniazid, Rifampin and Pyrazinamide)
No use of first-line anti-TB drugs within the last 8 weeks
Exclusion criteria:
Use of known hepatotoxic drugs (e.g., sodium valproate, methotrexate, sulfonamides)
Regular use of acetaminophen
Use of systemic glucocorticoids
Use of Silymarin-containing supplements within the last 4 weeks
Alcoholism
Use of antioxidant agents (e.g., vitamins E and C)
Having chronic hepatic or renal disease
Pregnancy
Lactation
Age
From 18 years old
Gender
Both
Phase
N/A
Groups that have been masked
Participant
Care provider
Investigator
Sample size
Target sample size:
53
Actual sample size reached:
37
Randomization (investigator's opinion)
Randomized
Randomization description
Simple randomization was used for patients' allocation to the groups. For this, an online random number generator was used (available at: https://www.random.org/sequences) so that even and odd numbers were considered for drug and control groups, respectively.
Blinding (investigator's opinion)
Double blinded
Blinding description
This study is a double-blind clinical trial (participant, researcher).
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethical Committee of Isfahan University of Medical Sciences
Street address
Isfahan University of Medical Sciences, Hezar-Jerib Ave.
City
Isfahan
Province
Isfehan
Postal code
8174673461
Approval date
2016-05-29, 1395/03/09
Ethics committee reference number
IR.MUI.REC.1395.3.930
Health conditions studied
1
Description of health condition studied
Anti-tuberculosis drugs-induced hepatotoxicity
ICD-10 code
K71
ICD-10 code description
Toxic liver disease
Primary outcomes
1
Description
Serum level of ALT
Timepoint
Before the intervention and 7 and 14 days after initiation of intervention
Method of measurement
blood test
2
Description
serum level of AST
Timepoint
Before the intervention and 7 and 14 days after initiation of intervention
Method of measurement
blood test
3
Description
serum level of ALP
Timepoint
Before the intervention and 7 and 14 days after initiation of intervention
Method of measurement
blood test
4
Description
serum level of bilirubin(direct/total)
Timepoint
Before the intervention and 7 and 14 days after initiation of intervention
Method of measurement
blood test
Secondary outcomes
empty
Intervention groups
1
Description
Intervention group: 150-mg oral capsules of Milk Thistle, twice daily, for 2 weeks with standard 4-drug anti-TB therapeutic regimen including isoniazid 5 mg/kg + rifampin 10 mg/kg + ethambutol 15 mg/kg + pyrazinamide 25 mg/kg
Category
Prevention
2
Description
Control group: standard 4-drug anti-TB therapeutic regimen including isoniazid 5 mg/kg + rifampin 10 mg/kg + ethambutol 15 mg/kg + pyrazinamide 25 mg/kg
Category
N/A
Recruitment centers
1
Recruitment center
Name of recruitment center
Al-Zahra Hospital
Full name of responsible person
Rasool Soltani
Street address
Soffeh Ave.
City
Isfahan
Province
Isfehan
Postal code
8174675731
Phone
+98 31 3620 2020
Email
soltani@pharm.mui.ac.ir
Web page address
https://icri.mui.ac.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Esfahan University of Medical Sciences
Full name of responsible person
Shagayegh Haghjooy Javanmard
Street address
Hezar-Jerib Ave.
City
Isfahan
Province
Isfehan
Postal code
81746-83461
Phone
+98 31 3668 8138
Email
sh_haghjoo@med.mui.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Esfahan University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Esfahan University of Medical Sciences
Full name of responsible person
Rasool Soltani
Position
Associate professor
Latest degree
Specialist
Other areas of specialty/work
Medical Pharmacy
Street address
Fculty of Pharmacy, Isfahan University of Medical Sciences, Hezar-Jerib Ave.
City
Isfahan
Province
Isfehan
Postal code
8176776161
Phone
+98 31 3786 5537
Email
soltani@pharm.mui.ac.ir
Person responsible for scientific inquiries
Contact
Name of organization / entity
Esfahan University of Medical Sciences
Full name of responsible person
Rasool Soltani
Position
Associate professor
Latest degree
Specialist
Other areas of specialty/work
Medical Pharmacy
Street address
Faculty of Pharmacy, Isfahan University of Medical Sciences, Hezar-Jerib Ave.
City
Isfahan
Province
Isfehan
Postal code
8176776161
Phone
+98 31 3786 5537
Email
soltani@pharm.mui.ac.ir
Person responsible for updating data
Contact
Name of organization / entity
Esfahan University of Medical Sciences
Full name of responsible person
Rasool Soltani
Position
Associate professor
Latest degree
Specialist
Other areas of specialty/work
Medical Pharmacy
Street address
Faculty of Pharmacy, Isfahan University of Medical Sciences, Hezar-Jerib Ave.
City
Isfahan
Province
Isfehan
Postal code
8176776161
Phone
+98 31 3786 5537
Email
soltani@pharm.mui.ac.ir
Sharing plan
Deidentified Individual Participant Data Set (IPD)
No - There is not a plan to make this available
Justification/reason for indecision/not sharing IPD