A Trial Of Intravenous N-Acetylcysteine In The Management Of Antituberculous Drug-Induced Hepatitis
- Conditions
- Drug-Induced Liver Injury
- Interventions
- Registration Number
- NCT02182167
- Lead Sponsor
- University of Cape Town
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 102
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Placebo Water Water IV NAC IV N-acetylcysteine (NAC) Participants will receive IV N-acetylcysteine or placebo. The dosing regimen is based on the regimens used in paracetamol poisoning . Initial dose: 150 mg/kg body mass of N-acetylcysteine/WFI infused in 200 mL of 5% dextrose intravenously over 60 minutes, followed by continuous infusion: 50 mg/kg body mass in 500 mL of 5% dextrose over next 4 hours, followed by 100 mg/kg body mass in 1 litre of 5% dextrose over 16 hours.
- Primary Outcome Measures
Name Time Method ALT normalisation up to 8 weeks To determine the effect of IV NAC on the time to normalization of liver function in patients with TB DIH
- Secondary Outcome Measures
Name Time Method Recovery from liver failure up to 8 weeks To determine the effect of IV NAC on the rate of recovery from liver failure
Duration of hospitalization up to 8 weeks To determine the effect of IV NAC on duration of hospitalization
All-cause mortality up to 8 weeks To determine the effect of IV NAC on all-cause mortality in patients with TB DIH
Adverse Events up to 8 weeks To determine the adverse event profile of IV NAC when administered to patients with TB DIH
TB Drug Rechallenge up to 8 weeks To determine the effect of IV NAC on success of TB drug rechallenge.
Rechallenge duration up to 8 weeks To determine the effect of IV NAC on duration of rechallenge
Trial Locations
- Locations (2)
Groote Schuur Hospital
🇿🇦Cape Town, Western Province, South Africa
New Somerset Hospital
🇿🇦Cape Town, Western Province, South Africa