None listed
Conditions
Brief summary
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.
Interventions
All participants in the study will be commenced on the standard acetylcysteine regimen. That is 200mg/kg acetylcysteine in 500mls 5% glucose over 4 hours followed by 100mg/kg acetylcysteine in 1000mls 5% glucose over 16 hours.
Participants randomised to the intervention arm will receive 12 hours of acetylcysteine only. To achieve this, they will have their 16 hour infusion of acetylcysteine ceased at eight hours (250mg/kg acetylcysteine) and then be commenced on the equivalent fluid and volume
All participants in the study will be commenced on the standard acetylcysteine regimen. That is 200mg/kg acetylcysteine in 500mls 5% glucose over 4 hours followed by 100mg/kg acetylcysteine in 1000mls 5% glucose over 16 hours. Participants randomised to the intervention arm will receive 12 hours of acetylcysteine only. To achieve this, they will have their 16 hour infusion of acetylcysteine ceased at eight hours (250mg/kg acetylcysteine) and then be commenced on the equivalent fluid and volume but not acetylcysteine for the remaining eight hours i.e. 500mL of 5% glucose over 8 hours. This is administered in an emergency department short stay/observation ward with 24/7 nursing care to monitor adherence to above intervention.
Sponsors
Colin Page
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1.Single immediate release paracetamol overdoses of 30g or less with an initial paracetamol concentration above but less than twice the nomogram line (paracetamol ratio <2) 2.Acetylcysteine can be safely commenced within 8 hours of ingestion. 3.Informed consent can be obtained. The paracetamol ratio is the first paracetamol concentration taken between four and 16 hours post ingestion divided by the paracetamol concentration on the 150mg/L at four-hour standard nomogram line at the same time point.
Exclusion criteria
1. Staggered or repeated immediate release paracetamol overdoses. 2. Single, staggered or repeated overdoses of sustained release paracetamol. 3. Repeated supratherapeutic ingestion of paracetamol. 4. Late presentation i.e. >8 hours since ingestion timea. 5. >30g paracetamolb or paracetamol ratio >2.
Outcome results
None listed