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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

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 Summary:

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.


Sponsor: University of Cape Town

Current Primary Outcome: 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


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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


Original Secondary Outcome: Same as current

Information By: University of Cape Town

Dates:
Date Received: June 18, 2014
Date Started: May 2014
Date Completion: June 2018
Last Updated: May 5, 2017
Last Verified: May 2017