Paracetamol overdose Injury, Occupational Diseases, Poisoning
Conditions
Interventions
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 acetylcys
Sponsors
Accord (United Kingdom)
Eligibility
Sex/Gender
All
Age
16 Years to 150 Years
Inclusion criteria
Inclusion criteria: 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)
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Glutathione (GSH) derived paracetamol metabolite concentration as a percentage of total metabolites (%GSH) in the circulation at the end of the infusion of the second NAC dose | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety: Incidence of adverse events and serious adverse events occurring from the time of starting NAC until the end of follow-up. There are expected adverse reactions listed in the product summary of product characteristics (SPC). The protocol defines two adverse events of special interest (AESI). Symptoms of anaphylactoid reactions reported on Likert scale at baseline and 12h after starting NAC. Efficacy: Full paracetamol metabolite panel (APAP-Cys, APAP-Glu, APAP-Sul, APAP-GSH, APAPMer) in serum and urine. Measured at baseline (pre-NAC) for serum and urine. For serum, at 12h after NAC started. All urine is collected for the trial period. ALT (gold standard diagnostic liver injury marker), high sensitivity liver injury markers (keratin-18, microRNA-122, GLDH) and INR (a prognostic marker of liver synthetic function) measured at baseline and after 12 hrs NAC from blood. Length of hospital admission, repeat hospital admission within 7 days, acute liver failure, transfer to Scottish Liver Transplantation Unit, liver transplantation and death recorded from medical notes at 7 days follow-up. | — |
Countries
Scotland, United Kingdom
Outcome results
None listed