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Trial registered on ANZCTR


Registration number
ACTRN12615000938505
Ethics application status
Approved
Date submitted
20/08/2015
Date registered
8/09/2015
Date last updated
19/11/2018
Date data sharing statement initially provided
19/11/2018
Date results information initially provided
19/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The NACSTOP trial: Investigation of the early cessation of N-acetylcysteine after paracetamol overdose.
Scientific title
Investigation of the early cessation of N-acetylcysteine versus standard care on liver injury after paracetamol overdose.
Secondary ID [1] 287323 0
Nil
Universal Trial Number (UTN)
U1111-1173-4474
Trial acronym
NACSTOP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Paracetamol overdose 295960 0
Condition category
Condition code
Mental Health 296237 296237 0 0
Suicide
Injuries and Accidents 296297 296297 0 0
Poisoning

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All patients with normal ALT and AST (within lab reference range) and paracetamol<132 micro mol/L, will be allocated to either intervention or control treatment.

200mg/kg of NAC intravenously over 4 hours, then 50mg/kg NAC over 8 hours intravenously then change to 1 litre of intravenous Compound serum Lactate over 8 hours if study criteria met at 12 hours (alanine transaminase and AST less than the upper limit of the lab reference range, paracetamol <132 micro mol/L) in intervention group. Bloods will then be repeated again at 20 hrs post initiation of NAC. A normal alanine transaminase indicates no sign of liver toxicity and low paracetamol concentration at less than therapeutic dose of paracetamol in the blood.

Lab reference range for ALT, AST will vary from institution but the higher end of the range is 50 IU/L.

Strategies to monitor medication adherence include observation in hospital of administration by medical and nursing staff, and computer logging of drug administration by nursing staff.
Intervention code [1] 292640 0
Treatment: Drugs
Intervention code [2] 292641 0
Prevention
Comparator / control treatment
200mg/kg of NAC intravenously over 4 hours and 100mg NAC intravenously over 16 hours. Normal ALT and AST and paracetamol concentrations <132 micromol/L at 12 hours of NAC will be included in the control treatment group.
Control group
Active

Outcomes
Primary outcome [1] 295899 0
Serum assay of alanine transaminase (ALT). ALT Doubling and ALT > 100 IU/L will be taken as hepatic injury.
Timepoint [1] 295899 0
20 hrs after initiation of NAC
Secondary outcome [1] 316884 0
Hepatotoxicity defined as ALT >1000 IU/L measured by serum assay
Timepoint [1] 316884 0
20 hrs after NAC initiated
Secondary outcome [2] 316885 0
Length of stay will be assessed by review of hospital records
Timepoint [2] 316885 0
This will be assessed from time of triage to discharge from hospital.

Eligibility
Key inclusion criteria
Single or staggered paracetamol overdose
Minimum age
16 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Not mentally competant
ALT or AST > lab reference range and/or paracetamol > 132 micromol/L at 12 hours post NAC initiation.
Participants will be enrolled prior to the blood tests at 12hrs post NAC treatment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 4251 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 4252 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [3] 4253 0
Casey Hospital - Berwick
Recruitment hospital [4] 4254 0
Dandenong Hospital - Dandenong
Recruitment hospital [5] 4255 0
Westmead Hospital - Westmead
Recruitment hospital [6] 4256 0
Blacktown Hospital - Blacktown

Funding & Sponsors
Funding source category [1] 291885 0
Government body
Name [1] 291885 0
Monash Health
Address [1] 291885 0
135 David St, Dandenong 3175, VIC
Country [1] 291885 0
Australia
Funding source category [2] 291964 0
Government body
Name [2] 291964 0
Austin Health
Address [2] 291964 0
145 Studley Road, Heidelberg 3084, VIC
Country [2] 291964 0
Australia
Primary sponsor type
Government body
Name
Monash Health
Address
135 David St, Dandenong 3175, VIC
Country
Australia
Secondary sponsor category [1] 290582 0
Government body
Name [1] 290582 0
Austin Health
Address [1] 290582 0
145 Studley Road, Heidelberg 3084, VIC
Country [1] 290582 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293392 0
Monash HREC
Ethics committee address [1] 293392 0
Ethics committee country [1] 293392 0
Date submitted for ethics approval [1] 293392 0
26/08/2015
Approval date [1] 293392 0
06/01/2016
Ethics approval number [1] 293392 0

Summary
Brief summary
The primary purpose of the study is to investigate whether ceasing the use of antidote (NAC) in patients presenting early with paracetamol overdose in a low risk population is feasible and safe.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 59702 0
Dr Anselm Wong
Address 59702 0
145 Studley Road, Heidelberg VIC 3084
Austin Hospital Emergency Department
Country 59702 0
Australia
Phone 59702 0
+613 94964509
Fax 59702 0
Email 59702 0
anselm.wong@austin.org.au
Contact person for public queries
Name 59703 0
Dr Anselm Wong
Address 59703 0
145 Studley Road, Heidelberg VIC 3084
Austin Hospital Emergency Department
Country 59703 0
Australia
Phone 59703 0
+613 9496 4509
Fax 59703 0
Email 59703 0
anselm.wong@austin.org.au
Contact person for scientific queries
Name 59704 0
Dr Anselm Wong
Address 59704 0
145 Studley Road, Heidelberg VIC 3084
Austin Hospital Emergency Department
Country 59704 0
Australia
Phone 59704 0
+613 9496 4509
Fax 59704 0
Email 59704 0
anselm.wong@austin.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 315 0
Hepatology. 2018 Aug 19. doi: 10.1002/hep.30224. [Epub ahead of print]
The NACSTOP trial: A multi-center, cluster-controlled trial of early cessation of acetylcysteine in acetaminophen overdose.
Wong A, McNulty R, Taylor DM, Sivilotti MLA, Greene S, Gunja N, Koutsogiannis Z, Graudins A.
Attachments [1] 315 0
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary