Volume 224 - Issue 1
Early Cessation of Acetylcysteine Treatment After Paracetamol Overdose (NACSTOP 2): A Non-Inferiority Randomised Controlled Trial
Authors: Anselm Wong, Richard McNulty, Sarah E. Hodgson, Naren Gunja, Andis Graudins
Correspondence: anselm.wong@austin.org.au
Med J Aust 2026 || doi: 10.5694/mja2.70114
Published online: 18 January 2026
Published online: 18 January 2026
Abstract
Objectives
To determine whether ceasing acetylcysteine treatment for adults with acute paracetamol overdose after at least 12h of the two-bag acetylcysteine regimen is non-inferior to providing the full 20-h two-bag regimen.
Study Design
Open label, non-inferiority randomised controlled trial.
Setting
Emergency departments of six Australian metropolitan hospitals (four in Melbourne, two in Sydney), 1 December 2019–31 July 2024.
Participants
Adults who required acetylcysteine treatment following single or staggered paracetamol ingestions whose serum alanine transaminase (ALT) level was below 40IU/L on presentation, and whose ALT levels were below 40IU/L and serum paracetamol concentrations below 20mg/L after 12 h of acetylcysteine treatment.
Intervention
Control group (standard care): two-bag intravenous acetylcysteine regimen (200mg/kg over 4h, followed by 100mg/kg over 16h). Intervention group: Acetylcysteine stopped at least 12h after treatment initiation and the 20-h infusion period completed with intravenous compound sodium lactate.
Main Outcome Measures
Difference in ALT level between presentation and 20h 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 3IU/L.
Results
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, 17years; interquartile range [IQR], 16–23years; 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 13h (IQR, 13–13 h). The median change in ALT level between arrival and 20h after starting intravenous acetylcysteine treatment was similar for the intervention (−1IU/L; IQR, −4 to 1IU/L) and control groups (0IU/L; IQR, −2 to 2IU/L); the difference in median change (−1IU/L; 95% CI, −2 to 1IU/L) was consistent with the non-inferiority criterion. No patients developed hepatic injury or hepatotoxicity.
Conclusion
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.
Trial Registration
ACTRN12619001549112 (prospective)