A Trial Of Intravenous N-Acetylcysteine In The Management Of Antituberculous Drug-Induced Hepatitis

Drug-Induced Liver Injury Clinical Trial

— NAC in TB DIH  

Official title:

A Randomised Controlled Trial of Intravenous N-acetylcysteine in the Management of Antituberculous Drug-induced Hepatitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02182167
• Other study ID #: 20130808
• Secondary ID: DOH-27-0414-4719
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: May 2014
• Est. completion date: February 2019

Study information

• Verified date: February 2019
• Source: University of Cape Town
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

We will conduct a randomized placebo controlled trial to determine whether administration of intravenous (IV) NAC to participants with TB DIH, in dosages similar to that used in paracetamol poisoning, can improve recovery from hepatotoxicity.

Description:

South Africa has a huge tuberculosis (TB) disease burden, with 948 per 100 000 people diagnosed with TB in 2008. TB drug induced hepatitis (DIH) is a common adverse effect of TB therapy that causes significant patient morbidity and prolonged hospital stays. N-Acetylcysteine (NAC) has been extensively studied and used for many years in the treatment of paracetamol-induced hepatotoxicity, with good evidence of efficacy and safety. NAC has also been used in other forms of liver injury and drug toxicity. It has not previously been used in the management of TB DIH.

We will screen all patients with clinical hepatitis on TB treatment admitted to New Somerset and Groote Schuur hospitals and aim to recruit 100 participants over 3 years. We will randomise 50 participants to receive an IV loading dose of 150mg/kg of NAC over 60 minutes followed by 50mg/kg IV over 4 hours by continuous infusion and finally 100mg/kg IV over 16 hours. Fifty participants will be randomised to receive placebo. The primary outcome will be time to normalisation of liver function (ALT<100). We will also determine the effect of NAC on duration of hospitalization, rate of recovery from liver failure, all cause mortality, and describe adverse effects of IV NAC in this patient population.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: February 2019
• Est. primary completion date: February 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults > 18 years old

• Diagnosed with pulmonary or extrapulmonary tuberculosis based on symptoms, radiological features and/or laboratory evidence.

• On first line antituberculous therapy

• Diagnosed with TB DIH

Exclusion Criteria:

• Patients with a diagnosis of acute viral hepatitis based on a positive anti-HAV, IgM, anti- HBcIgM, or confirmed hepatitis C infection

• Patients known to be asthmatic

Related Conditions & MeSH terms

• Chemical and Drug Induced Liver Injury
• Drug-Induced Liver Injury
• Hepatitis

Intervention

Drug:
• IV N-acetylcysteine (NAC)

• Water

Locations

Country	Name	City	State
South Africa	Groote Schuur Hospital	Cape Town	Western Province
South Africa	New Somerset Hospital	Cape Town	Western Province

Sponsors (2)

Lead Sponsor	Collaborator
University of Cape Town	Medical Research Council, South Africa

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Biomarkers	To store blood, urine and biopsy specimens (if biopsies were taken as part of patient management),bank serum, to enable us to conduct future sub studies exploring mechanisms, predictors and biomarkers of TB DIH, genetic associations with TB DIH and improved diagnostic strategies
Primary	ALT normalisation	To determine the effect of IV NAC on the time to normalization of liver function in patients with TB DIH	up to 8 weeks
Secondary	Duration of hospitalization	To determine the effect of IV NAC on duration of hospitalization	up to 8 weeks
Secondary	Recovery from liver failure	To determine the effect of IV NAC on the rate of recovery from liver failure	up to 8 weeks
Secondary	All-cause mortality	To determine the effect of IV NAC on all-cause mortality in patients with TB DIH	up to 8 weeks
Secondary	Adverse Events	To determine the adverse event profile of IV NAC when administered to patients with TB DIH	up to 8 weeks
Secondary	TB Drug Rechallenge	To determine the effect of IV NAC on success of TB drug rechallenge.	up to 8 weeks
Secondary	Rechallenge duration	To determine the effect of IV NAC on duration of rechallenge	up to 8 weeks