Clinical trial NCT02182167: A Trial Of Intravenous N-Acetylcysteine In The Management Of Antituberculous Drug-Induced Hepatitis
Official title: A Randomised Controlled Trial of Intravenous N-acetylcysteine in the Management of Antituberculous Drug-induced Hepatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Drug-Induced Liver Injury
Keywords: Drug Induced Hepatitis (DIH)
Toxic Liver
Drug Induced Liver Injury (DILI)
Lead sponsor: University of Cape Town
Sponsor class: OTHER
Collaborators: name: Medical Research Council, South Africa
First posted: 2014-07-08
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: ALT normalisation
timeFrame: up to 8 weeks
Secondary outcomes:
measure: Duration of hospitalization
timeFrame: up to 8 weeks
measure: Recovery from liver failure
timeFrame: up to 8 weeks
measure: All-cause mortality
timeFrame: up to 8 weeks
measure: Adverse Events
timeFrame: up to 8 weeks
measure: TB Drug Rechallenge
timeFrame: up to 8 weeks
measure: Rechallenge duration
timeFrame: up to 8 weeks
Other outcomes:
measure: Biomarkers
Locations:
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital
state: Western Province
city: Cape Town
country: South Africa
facility: New Somerset Hospital
state: Western Province
Study officials:
affiliation: University of Cape Town
name: Karen Cohen
role: PRINCIPAL_INVESTIGATOR
References: