A Randomised Controlled Trial of Intravenous N-acetylcysteine in the Management of Antituberculous Drug-induced Hepatitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 102
- 试验地点
- 2
- 主要终点
- ALT normalisation
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: IV N-acetylcysteine (NAC) (Drug)
Placebo
Water
干预措施: Water (Drug)
结局指标
主要结局
ALT normalisation
时间窗: up to 8 weeks
To determine the effect of IV NAC on the time to normalization of liver function in patients with TB DIH
次要结局
- Recovery from liver failure(up to 8 weeks)
- Adverse Events(up to 8 weeks)
- Duration of hospitalization(up to 8 weeks)
- All-cause mortality(up to 8 weeks)
- TB Drug Rechallenge(up to 8 weeks)
- Rechallenge duration(up to 8 weeks)
研究者
Dr Karen Cohen
Dr Karen Cohen
University of Cape Town