The Efficacy of Silymarin on the Prevention of Hepatotoxicity From Antituberculosis Drugs

Study Overview
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Brief Summary
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Hepatitis is one of the most common adverse effect from anti-tuberculosis. Silymarin showed its efficacy to decreased serum alanine transaminase enzyme in animal models from recent study. No confirmed this efficacy was performed in human. A prospective, double-blind, placebo-controlled trial was carried out according to Good Clinical Practice Guideline. This study is to define the efficacy of silymarin to prevent hepatotoxicity from anti-tuberculosis drugs. Informed consent is obtained prior to the study. New patients diagnosed with tuberculosis are enrolled. Patients with liver diseases, current alcohol drinking more than 20 g/day, regular use of herbal or other potential hepatotoxic drugs are excluded. Patients are treated with a standard regimen of four anti-tuberculosis therapy. They will randomize to receive either placebo or silymarin (140 mg) thrice daily. Liver function test (LFT) and clinical changes are assessed at 2- and 4-week after initiation of the treatment. DILI from anti-tuberculosis drugs ('atb-DILI') is defined as: i) a rise of alanine aminotransferase (ALT) to 2 times above normal upper limit, or ii) an elevation of total bilirubin more than 2 mg/dl with or without ALT elevation. The study endpoints are the level of ALT by week 4 and the number of patients who developed atb-DILI. Statistical analysis is used to compare the differences in ALT and number of atb-DILI

Detailed Description
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- Prevention of antituberculosis-related drug induced liver injury with silymarin is investigated.

Official Title
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The Efficacy of Silymarin on the Prevention of Hepatotoxicity From Antituberculosis Drugs

Conditions
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Tuberculosis

Intervention / Treatment
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* Drug: silymarin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: tuberculosis cases treated with isoniazid, rifampicin, ethambutol and pyrazinamide Exclusion Criteria: no known liver disease (HBV, HCV), and HIV infection normal ALT level before enrollment refuse to participate

Ages Eligible for Study
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Minimum Age: 18 Years

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: silymarin<br>Silymarin 140 mg three times a day for 4 weeks | Drug: silymarin<br>* 140 mg three times a day for 4 weeks<br>|
| Placebo Comparator: placebo<br>Placeo 1 tab three times a day for 4 weeks | Drug: Placebo<br>* Placebo (silymarin) 1 tab three times a day for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of patients who develop drug-induced liver injury (DILI) at 4 weeks | DILI from anti-tuberculosis drugs ('atb-DILI') is defined as: i) a rise of alanine aminotransferase (ALT) to 2 times above normal upper limit, or ii) an elevation of total bilirubin more than 2 mg/dl with or without ALT elevation. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug-induced liver injury, Tuberculosis, Silymarin