None listed
Conditions
Brief summary
Paracetamol poisoning can cause liver injury; the mainstay of treatment is administration of the antidote acetylcysteine. There is a subgroup of paracetamol poisoned patients who develop liver injury despite standard treatment. Fomepizole has been proposed as an antidote due to its ability to inhibit production of paracetamol’s toxic metabolite. However, the clinical evidence for its use is limited. Hence in this study we will utilise a healthy human volunteer simulated overdose crossover model. Each volunteer will serve as their own control. We will examine both immediate and modified release paracetamol formulations at a dose of 80mg/kg. We will investigate the efficacy of fomepizole at 2 hours post ingestion. If there is a significant effect we will then examine fomepizole at 4h. This study aims to provide valuable information on the potential use of fomepizole as an antidote for paracetamol poisoning.
Interventions
Participants will receive a single dose of oral paracetamol tablets 80 mg/kg, and intravenous fomepizole (15mg/kg) administered 2 hours post paracetamol ingestion.
Both immediate-release and modified-release paracetamol will be tested. Participants may participate in both or just one preparation. If they cross-over there will be at least a 2 week wash-out. There is also a 2 week washout between treatment arm and control.
The investigator will supervise and observe the participant swallow the
Participants will receive a single dose of oral paracetamol tablets 80 mg/kg, and intravenous fomepizole (15mg/kg) administered 2 hours post paracetamol ingestion. Both immediate-release and modified-release paracetamol will be tested. Participants may participate in both or just one preparation. If they cross-over there will be at least a 2 week wash-out. There is also a 2 week washout between treatment arm and control. The investigator will supervise and observe the participant swallow the paracetamol.
Sponsors
Prince of Wales Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
- Adults at least 18 years of age - No underlying liver disease (baseline liver function tests to be performed after recruitment) - No regular medications except for vitamins or oral contraceptive pill - No history of chronic alcohol, tobacco (smoker), or illicit drug use. - Weigh less than 100 kg and BMI < 29 kg/m2
Exclusion criteria
- Pregnancy or lactation, - Allergy to the medications administered in the study (paracetamol and fomepizole) - Weight > 100kg or body mass index (BMI) > 29 kg/ m2 as obesity appears to increase activity of CYP2E1 and there are concerns of increased toxicity of paracetamol in the setting of non-alcoholic fatty liver disease. - Pregnancy (females of child-bearing age to have urine BHCG). - Pre-existing liver disease, - Chronic alcohol consumption greater than 20 g per day, - Any chronic illness, - On regular medications (except for vitamins or the oral contraceptive pill) - Before participation in the study, if on screening tests any abnormality in liver function tests performed 1 week before the study and 3 days after the first arm of the study.
Outcome results
None listed