Early Cessation of Acetylcysteine Treatment After Paracetamol Overdose (NACSTOP 2): A Non-Inferiority Randomised Controlled Trial.

Abstract

To determine whether ceasing acetylcysteine treatment for adults with acute paracetamol overdose after at least 12 h of the two-bag acetylcysteine regimen is non-inferior to providing the full 20-h two-bag regimen. Open label, non-inferiority randomised controlled trial. Emergency departments of six Australian metropolitan hospitals (four in Melbourne, two in Sydney), 1 December 2019-31 July 2024. Adults who required acetylcysteine treatment following single or staggered paracetamol ingestions whose serum alanine transaminase (ALT) level was below 40 IU/L on presentation, and whose ALT levels were below 40 IU/L and serum paracetamol concentrations below 20 mg/L after 12 h of acetylcysteine treatment. Control group (standard care): two-bag intravenous acetylcysteine regimen (200 mg/kg over 4 h, followed by 100 mg/kg over 16 h). Intervention group: Acetylcysteine stopped at least 12 h after treatment initiation and the 20-h infusion period completed with intravenous compound sodium lactate. Difference in ALT level between presentation and 20 h after acetylcysteine treatment initiation; non-inferiority was defined as the upper limit of the 95% confidence interval (CI) of the difference between median changes in ALT level for the intervention and control groups being less than 3 IU/L. Of 2830 people who presented with paracetamol overdose, 860 received acetylcysteine treatment; 186 people who met both the presentation and 12-h acetylcysteine treatment blood test inclusion criteria (median age, 17 years; interquartile range [IQR], 16-23 years; 162 women [87%]) were randomly assigned to the intervention (93 participants) and control groups (93 participants). Median acetylcysteine infusion time in the intervention group was 13 h (IQR, 13-13 h). The median change in ALT level between arrival and 20 h after starting intravenous acetylcysteine treatment was similar for the intervention (-1 IU/L; IQR, -4 to 1 IU/L) and control groups (0 IU/L; IQR, -2 to 2 IU/L); the difference in median change (-1 IU/L; 95% CI, -2 to 1 IU/L) was consistent with the non-inferiority criterion. No patients developed hepatic injury or hepatotoxicity. An abbreviated acetylcysteine treatment regimen was non-inferior to the standard 20-h two-bag regimen for people with paracetamol overdose who were at low risk of hepatic failure. ACTRN12619001549112 (prospective).