A Trial Of Intravenous N-Acetylcysteine In The Management Of Antituberculous Drug-Induced Hepatitis (NAC in TB DIH)
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|ClinicalTrials.gov Identifier: NCT02182167|
Recruitment Status : Recruiting
First Posted : July 8, 2014
Last Update Posted : October 11, 2018
|Condition or disease||Intervention/treatment||Phase|
|Drug-Induced Liver Injury||Drug: IV N-acetylcysteine (NAC) Drug: Water||Phase 2 Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomised Controlled Trial of Intravenous N-acetylcysteine in the Management of Antituberculous Drug-induced Hepatitis|
|Actual Study Start Date :||May 2014|
|Estimated Primary Completion Date :||March 2019|
|Estimated Study Completion Date :||August 2019|
Experimental: IV 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.
Drug: IV N-acetylcysteine (NAC)
Other Name: Paradote
Placebo Comparator: Placebo
- ALT normalisation [ Time Frame: up to 8 weeks ]To determine the effect of IV NAC on the time to normalization of liver function in patients with TB DIH
- Duration of hospitalization [ Time Frame: up to 8 weeks ]To determine the effect of IV NAC on duration of hospitalization
- Recovery from liver failure [ Time Frame: up to 8 weeks ]To determine the effect of IV NAC on the rate of recovery from liver failure
- All-cause mortality [ Time Frame: up to 8 weeks ]To determine the effect of IV NAC on all-cause mortality in patients with TB DIH
- Adverse Events [ Time Frame: up to 8 weeks ]To determine the adverse event profile of IV NAC when administered to patients with TB DIH
- TB Drug Rechallenge [ Time Frame: up to 8 weeks ]To determine the effect of IV NAC on success of TB drug rechallenge.
- Rechallenge duration [ Time Frame: up to 8 weeks ]To determine the effect of IV NAC on duration of rechallenge
- BiomarkersTo 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02182167
|Groote Schuur Hospital||Recruiting|
|Cape Town, Western Province, South Africa, 7925|
|Sub-Investigator: Farouk M Chughlay|
|Sub-Investigator: Mashiko Setshedi|
|Sub-Investigator: Gary Maartens|
|Sub-Investigator: Mark Sonderup|
|Sub-Investigator: Wendy Spearman|
|Principal Investigator: Karen Cohen|
|Sub-Investigator: Hannah Gunter|
|New Somerset Hospital||Recruiting|
|Cape Town, Western Province, South Africa, 8005|
|Sub-Investigator: Shiraz Moosa|
|Sub-Investigator: Dave Stead|
|Principal Investigator:||Karen Cohen||University of Cape Town|