HiSNAP
Research type
Research Study
Full title
A multi-centre, randomised, open label, blinded end-point, safety and efficacy trial of conventional (300 mg/kg) versus higher doses of acetylcysteine (450 mg/kg and 600 mg/kg) in patients with paracetamol overdose (HiSNAP Trial)
IRAS ID
1007520
Contact name
James Dear
Contact email
Sponsor organisation
University of Edinburgh
ISRCTN Number
ISRCTN17516192
Research summary
Paracetamol overdose is very common. Someone presents to hospital following an overdose every 5 minutes across the UK. This rate is the same as for heart attacks. Despite having an effective antidote called acetylcysteine (NAC), 1 in 10 patients go on to develop liver damage. NAC causes side-effects such as allergic reactions that are unpleasant for the patient and may result in this essential treatment being stopped. It is unknown whether increasing the dose of NAC is more effective at preventing liver damage partly because, until recently, dose increases have not been possible due to the side-effects. To address this, we designed a new protocol for giving NAC (the SNAP regimen) that is now used across the UK and has dramatically reduced the risk of patients experiencing side-effects. The improved safety of the SNAP regimen allows us to look at the potential benefits of treating patients with higher NAC doses. This trial will determine whether increasing the NAC dose results in an increase in the breakdown of paracetamol, without causing an unacceptable rate of side-effects. The trial aims to recruit 90 participants who have had a paracetamol overdose from the Emergency Department in NHS Lothian. The trial will compare the effects of NAC given for 12 hours at 1.5 times and double the standard dose with standard treatment (dose groups: standard = 300 mg/kg; 1.5 = 450 mg/kg and double=600 mg/kg). Paracetamol breakdown will be assessed by measurement of the breakdown products (metabolites) in the blood. Side-effects will be assessed using a patient questionnaire. Participants will be followed up for 7 days using their medical notes to review their recovery. The results of this trial are essential information for the next step, a UK-wide trial to determine whether a higher dose of NAC improves the outcome for patients.
REC name
East Midlands - Derby Research Ethics Committee
REC reference
23/EM/0129
Date of REC Opinion
26 Sep 2023
REC opinion
Further Information Favourable Opinion