HiSNAP trial-a multicentre, randomised, open-label, blinded end point, safety and efficacy trial of conventional (300 mg/kg) versus higher doses of acetylcysteine (450 mg/kg and 600 mg/kg) in patients with paracetamol overdose in the UK: study protocol
Abstract
Introduction: In overdose, a larger proportion of paracetamol (acetaminophen) is converted in the liver to the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). Glutathione (GSH) is the endogenous antioxidant that protects cells from NAPQI-induced injury. In overdose, GSH stores may become depleted, leaving NAPQI free to produce liver damage. N-Acetylcysteine (NAC) helps prevent paracetamol toxicity by replenishing liver GSH. This protective effect of NAC produces specific metabolites in the circulation. Currently, regardless of the paracetamol dose ingested, patients in the UK receive a dose of NAC based only on their weight. Basic pharmacology, mathematical modelling and observational studies suggest that this dose may be insufficient in some patients (particularly those taking a large overdose).
Methods and analysis: A multicentre trial, taking place across several hospitals in Scotland, UK, within Emergency Departments and Acute Medical Units. Recruitment commenced on 19 February 2024 and is anticipated to run for approximately 2 years. This is a three-group dose-finding trial, in which participants are assigned in a 1:1:1 ratio to either Standard NAC (300 mg/kg) or higher doses of 450 mg/kg (Group 1) and 600 mg/kg (Group 2). The primary outcome is the proportion of paracetamol metabolites in the circulation that are directly produced by GSH/NAC detoxification of NAPQI. A higher proportion of these metabolites will indicate that the additional NAC is reducing the…
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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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