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

NCT ID: NCT02182167

Last Updated: 2019-02-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 102 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2019-02-28

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.

Conditions

Drug-Induced Liver Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

IV N-acetylcysteine (NAC)

Intervention Type: DRUG

Placebo

Water

Group Type: PLACEBO_COMPARATOR

Water

Intervention Type: DRUG

Interventions

IV N-acetylcysteine (NAC)

Intervention Type: DRUG

Water

Intervention Type: DRUG

Other Intervention Names

Paradote

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical Research Council, South Africa

OTHER

Sponsor Role: collaborator

University of Cape Town

OTHER

Sponsor Role: lead

Responsible Party

Dr Karen Cohen

Dr Karen Cohen

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Karen Cohen

Role: PRINCIPAL_INVESTIGATOR

University of Cape Town

Locations

Groote Schuur Hospital

Cape Town, Western Province, South Africa

New Somerset Hospital

Cape Town, Western Province, South Africa

Countries

South Africa

Other Identifiers

DOH-27-0414-4719.

Identifier Type: REGISTRY

Identifier Source: secondary_id

20130808

Identifier Type: -

Identifier Source: org_study_id