A comparison of two different durations of the antidote acetylcysteine for paracetamol overdose.

Paracetamol is one of the commonest medications taken in overdose worldwide and is the leading cause of acute liver failure in the developed world. The antidote acetylcysteine which replenishes liver glutathione was developed in the 1970’s however the regimen (20 hours duration) was never subjected to either a randomised controlled trial or any dose ranging studies. The regimen gives a large loading dose and the remainder of the infusion (20 hours) is given to mirror the average time taken for paracetamol to be cleared by the liver. This time is only an average and depends on the degree of liver damage. We now know that this half-life is variable. For normal or undamaged livers it is much shorter (12 hours). The aim of the study is to compare acetylcysteine given over 20 hours compared to 12 hours for patients presenting early with paracetamol overdose to see if it provides the same protection against liver damage. The research design will be a multicentre non inferiority per protocol unblinded randomised controlled trial of a 20 hour versus a 12 hour regimen of acetylcysteine in paracetamol overdose. The study will be undertaken at the Princes Alexandra, Calvary Mater Newcastle and Prince of Wales hospitals. Eligible patients will be paracetamol overdoses less than 30g presenting within 8 hours of ingestion. The primary outcome will be a comparison between the standard and the experimental arm of the absolute difference between the liver function test alanine aminotransferase (ALT) on admission and 24 hours post ingestion. This difference will be analysed per protocol by student’s t­test or non­parametric equivalent depending on the distribution of the data.