A multi-centre, 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 (HiSNAP)
Paracetamol overdose
Participants will receive a 12-hour infusion of acetylcysteine (NAC) of either conventional (300 mg/kg), 1.5 times (450 mg/kg) or double (600 mg/kg) the conventional dose. Any preparation of acetylcysteine which has marketing authorisation in the UK to be used for this indication and is stocked by local hospital pharmacies at the participating sites may be prescribed in this study. Standard dosing (300 mg/kg) will be infused as per the SNAP regime: initial loading dose (100 mg/kg in 200 mL) given intravenously over 2h, followed by a second dose (200 mg/kg in 1000 mL) infused over 10h. OR HiSNAP group 1 (450 mg/kg): initial loading dose (150 mg/kg in 200 mL) given intravenously over 2h, followed by a second dose (300 mg/kg in 1000 mL) infused over 10h. OR HiSNAP group 2 (600 mg/kg): initial loading dose (200 mg/kg in 200 L) given intravenously over 2h, followed by a second dose (400 mg/kg in 1000 mL) infused over 10h. The dose of NAC assigned to each patient will be randomised using a centralised online randomisation system. Participants will be followed-up for 7 days following the infusion using their medical notes to review.
Current participant inclusion criteria as of 25/10/2024: 1. Paracetamol overdose* presenting to hospital within 24 hours of taking their last dose of paracetamol. *All patterns of overdose (single, staggered overdoses and therapeutic excess); Accidental or deliberate; Paracetamol alone or mixtures of tablets are eligible. 2. Patient deemed to need NAC treatment by the clinical team 3. Blood paracetamol concentration and ALT results are available (clinical care bloods) 4. Provision of informed consent 5. Adult (16 years old or above) Previous participant inclusion criteria: 1. Single acute paracetamol overdose presenting to hospital within 24h of overdose. All tablets ingested over a period of 2 h or less. Accidental or deliberate overdoses are eligible. Overdose of paracetamol alone or mixtures of tablets are eligible. 2. Overdose at risk of toxicity: blood paracetamol concentration over ‘200 line’ on nomogram 3. Provision of informed consent 4. Adult (16 years old or above)
Current participant exclusion criteria as of 25/10/2024: 1. Patients who do not have the capacity to consent 2. Patients who are pregnant or breastfeeding 3. Patients who have previously participated in the study 4. Patients who, in the opinion of the responsible clinician/nurse, are unlikely to complete the full course of NAC e.g. expressing wish to self-discharge 5. Patients detained under the Mental Health Act 6. Patients already started on NAC treatment 7. Patients with known viral hepatitis or HIV 8. Prisoners Previous participant exclusion criteria: 1. Patients who do not have the capacity to consent 2. Patients who are pregnant or breastfeeding 3. Patients who have previously participated in the study 4. Patients who, in the opinion of the responsible clinician/nurse, are unlikely to complete the full course of NAC e.g. expressing a wish to self-discharge 5. Patients detained under the Mental Health Act 6. Patients already started on NAC treatment 7. Known overdose of a modified/extended-release preparation of paracetamol 8. Patients with known viral hepatitis or HIV