Global 
Deutschland Liver and Bile
J Hepatol. 2025;83(4):881-887
A non-inferiority randomised controlled trial of a shorter acetylcysteine regimen for paracetamol overdose – The SARPO trial
Background and aims: Paracetamol is a commonly overdosed medication worldwide. Early acetylcysteine treatment can prevent hepatotoxicity. Multiple intravenous acetylcysteine regimens exist; the commonest recommending 300 mg/kg over 20 h. The authors investigated the effectiveness and safety of a shorter regimen in paracetamol overdoses ≤ 30 g.
Methods: In a multicentre, non-inferiority, randomised-controlled trial performed at three hospitals, 204 patients with acute paracetamol overdose ≤ 30 g, presenting within 8 h, were randomised to the standard 20 h acetylcysteine (200 mg/kg/4 h, 100 mg/kg/16 h) regimen or a short 12 h acetylcysteine (200 mg/kg/4 h, 50 mg/kg/8 h) regimen. The primary outcome was the absolute difference between alanine aminotransferase (ALT) 24 h post-ingestion and at admission (ΔALT24). Secondary outcomes included ALT > 150 U/L and ≥ 2x admission value at 24 h, systemic hypersensitivity and gastrointestinal adverse effects.
Results: The two groups were similar in terms of age, gender, dose ingested, paracetamol concentration, baseline ALT, hospital, charcoal administration and time until acetylcysteine treatment. The shorter regimen was non-inferior to the standard regimen. The median ΔALT24 for 107 patients given the shorter regimen was -2 U/L (IQR, -7 to 1 U/L) compared to -1 U/L (IQR, -5 to 1.5 U/L) for the 97 patients given the standard regimen; difference in medians of -1 U/L (95% CI: -3 to 1 U/L) were less than the upper non-inferiority margin of 5. No patient receiving the shorter regimen had a 24 h ALT of ≥ 2x admission value and > 150 U/L, compared to one receiving the standard regimen. No patient had an ALT > 1,000 U/L. The frequency of systemic hypersensitivity reactions was similar between groups (9/107 [8%] for short vs. 10/97 [10%] for standard regimens). Gastrointestinal adverse effects occurred in 78/107 patients (73%) receiving the short vs. 63/97 (65%) receiving the standard regimen.
Conclusions: The shorter 12 h acetylcysteine regimen had the same effectiveness and safety as the standard 20 h regimen in acute paracetamol overdoses ≤ 30 g, almost halving the length of treatment required.