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

NCT01800487 | Completed

• 1 other identifier: Ramathibodi_silymarin
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Tuberculosis

Keywords

Drug-induced liver injury; Tuberculosis; Silymarin

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

silymarin

ACTIVE COMPARATOR

Silymarin 140 mg three times a day for 4 weeks

Drug: silymarin

placebo

PLACEBO COMPARATOR

Placeo 1 tab three times a day for 4 weeks

Drug: Placebo

Interventions

silymarin DRUG

140 mg three times a day for 4 weeks

silymarin

Placebo DRUG

Placebo (silymarin) 1 tab three times a day for 4 weeks

placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• tuberculosis cases
• treated with isoniazid, rifampicin, ethambutol and pyrazinamide

You may not qualify if:

• no known liver disease (HBV, HCV), and HIV infection
• normal ALT level before enrollment
• refuse to participate

Sponsors & Collaborators

• Ramathibodi Hospital: lead

Study Sites (1)

Gastroenterology and Hepatology, Ramathibodi hospital

Bangkok, Bangkok, 10400, Thailand

Location

Related Publications (1)

• Luangchosiri C, Thakkinstian A, Chitphuk S, Stitchantrakul W, Petraksa S, Sobhonslidsuk A. A double-blinded randomized controlled trial of silymarin for the prevention of antituberculosis drug-induced liver injury. BMC Complement Altern Med. 2015 Sep 23;15:334. doi: 10.1186/s12906-015-0861-7.

  PMID: 26400476 DERIVED

MeSH Terms

Conditions

Tuberculosis; Chemical and Drug Induced Liver Injury

Interventions

Silymarin

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Liver Diseases; Digestive System Diseases; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Poisoning

Intervention Hierarchy (Ancestors)

Flavonolignans; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Abhasnee Sobhonslidsuk, MD

  Ramathibodi Hospital

  STUDY DIRECTOR

• Chote Luangchosiri, MD

  Ramathibodi

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: February 21, 2013
• First Posted: February 27, 2013
• Study Start: January 1, 2012
• Primary Completion: June 1, 2013
• Study Completion: July 1, 2013
• Last Updated: December 24, 2013

Record last verified: 2013-12

Locations

TH (1)