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Trial registered on ANZCTR


Registration number
ACTRN12617000973314
Ethics application status
Approved
Date submitted
23/06/2017
Date registered
6/07/2017
Date last updated
14/02/2019
Date data sharing statement initially provided
14/02/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Efficacy of a two bag N-acetylcysteine(NAC) regimen to treat paracetamol overdose (2NAC study).
Scientific title
Efficacy of a two bag N-acetylcysteine(NAC) regimen to treat paracetamol overdose (2NAC study)
Secondary ID [1] 292268 0
None
Universal Trial Number (UTN)
Trial acronym
2 NAC study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
paracetamol overdose 303790 0
Condition category
Condition code
Mental Health 303159 303159 0 0
Suicide
Oral and Gastrointestinal 303160 303160 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Acetylcysteine intravenously (200mg/kg over 4 hours followed immediately by 100mg/kg over 16 h0urs)

For patients requiring treatment with antidote post paracetamol overdose.
Intervention code [1] 298446 0
Not applicable
Comparator / control treatment
Acetylcysteine intravenously (150 mg/kg over 0.25 to 1 hour, 50 mg/kg over 4 hours, 100mg/kg over 16 hours)

For patients requiring treatment with antidote post paracetamol overdose.

Historical control: Between 1980 and 2005 - Canadian Acetaminophen Overdose Study
Control group
Historical

Outcomes
Primary outcome [1] 302528 0
The primary outcome will be the rate of acute liver injury (defined as peak Alanine transaminase (ALT)>150 IU/L and double baseline) stratified by time to first presentation bloods (<8 hrs or >8hrs). This will be assessed using serum samples.
Timepoint [1] 302528 0
During hospital admission.
Secondary outcome [1] 336314 0
Development of hepatotoxicity (alanine transaminase:ALT > 1000 IU/L). This will be assessed using serum samples.
Timepoint [1] 336314 0
During hospital admission

Eligibility
Key inclusion criteria
All paracetamol overdose treated with acetylcysteine
Minimum age
No limit
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
No treatment with acetylcysteine or overdose of paracetamol.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Both
Statistical methods / analysis
Descriptive data and proportions will be used in the study. Means (95%CI) or median (IQR) will be reported and the student t-test or the Mann Whitney U test will be used to analyze unpaired continuous data as indicated. The Chi square will be used to analyse unpaired categorical data.
Statistical significance will be recognized at <0.05.

Recruitment
Recruitment status
Recruiting
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,QLD,VIC
Recruitment hospital [1] 8433 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 8434 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [3] 8435 0
Casey Hospital - Berwick
Recruitment hospital [4] 8436 0
Dandenong Hospital - Dandenong
Recruitment hospital [5] 8437 0
Prince of Wales Hospital - Randwick
Recruitment hospital [6] 8438 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [7] 8439 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [8] 8440 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [9] 8441 0
Westmead Hospital - Westmead
Recruitment hospital [10] 8442 0
Blacktown Hospital - Blacktown
Recruitment postcode(s) [1] 16505 0
3084 - Heidelberg
Recruitment postcode(s) [2] 16506 0
3168 - Clayton
Recruitment postcode(s) [3] 16507 0
3806 - Berwick
Recruitment postcode(s) [4] 16508 0
3175 - Dandenong
Recruitment postcode(s) [5] 16509 0
2031 - Randwick
Recruitment postcode(s) [6] 16510 0
4102 - Woolloongabba
Recruitment postcode(s) [7] 16511 0
2298 - Waratah
Recruitment postcode(s) [8] 16512 0
2050 - Camperdown
Recruitment postcode(s) [9] 16513 0
2145 - Westmead
Recruitment postcode(s) [10] 16514 0
2148 - Blacktown

Funding & Sponsors
Funding source category [1] 296815 0
Hospital
Name [1] 296815 0
Monash Health
Address [1] 296815 0
Clayton Road, Clayton, Victoria 3168
Country [1] 296815 0
Australia
Primary sponsor type
Hospital
Name
Monash Health
Address
Clayton Road, Clayton, Victoria 3168
Country
Australia
Secondary sponsor category [1] 295805 0
None
Name [1] 295805 0
Address [1] 295805 0
Country [1] 295805 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298051 0
Monash Health HREC
Ethics committee address [1] 298051 0
Clayton Road, Clayton, Victoria 3168
Ethics committee country [1] 298051 0
Australia
Date submitted for ethics approval [1] 298051 0
Approval date [1] 298051 0
24/04/2017
Ethics approval number [1] 298051 0

Summary
Brief summary
Paracetamol overdose is the most common pharmaceutical poisoning in developed countries and its incidence is increasing in the developing world. Overdose can lead to liver failure, and in the worst circumstances, death. In overdose, the increased production of N-acetyl para-benzoquinoneimine (NAPQI) depletes hepatic glutathione stores and eventually causes hepatocyte injury. Acetylcysteine is administered as the antidote to prevent hepatotoxicity in overdose. The typical three-bag infusion-dosing regimen in Australia is 150 mg/kg over 1 hour, 50 mg/kg over 4 hours and 100 mg/kg over 16 hours.
Despite the safety of this regimen, there remains a significant amount of adverse reactions to acetylcysteine and delays between infusions. To this effect, a recent study of over 200 patients who received a two-bag acetylcysteine regimen was recently undertaken. A 200mg/kg loading dose of NAC was infused over four hours with a further 100 mg/kg infused over 16-hours. The incidence and severity of adverse reactions was significantly reduced, compared to the three-bag regimen, from 10% to 4.3%. A similar two-bag regimen has been adopted by various hospitals around Australia.

The efficacy of this new two-bag regimen has not been determined. We aim to compare the rate of acute liver injury using a two-bag acetylcysteine regimen and compare this to the three-bag regimen in the setting of paracetamol overdose.
Trial website
Trial related presentations / publications
Public notes
Ethics obtained from Feb 2014 from Monash Health to 24/4/17. Multicentre study approved thereafter.

Contacts
Principal investigator
Name 75822 0
Dr Anselm Wong
Address 75822 0
c/o Emergency Department
Austin Health
Heidelberg 3084
Victoria
Country 75822 0
Australia
Phone 75822 0
+61 394965000
Fax 75822 0
Email 75822 0
anselm.wong@austin.org.au
Contact person for public queries
Name 75823 0
Dr Anselm Wong
Address 75823 0
c/o Emergency Department
Austin Health
Heidelberg 3084
Victoria
Country 75823 0
Australia
Phone 75823 0
+61 394965000
Fax 75823 0
Email 75823 0
anselm.wong@austin.org.au
Contact person for scientific queries
Name 75824 0
Dr Anselm Wong
Address 75824 0
c/o Emergency Department
Austin Health
Heidelberg 3084
Victoria
Country 75824 0
Australia
Phone 75824 0
+61 394965000
Fax 75824 0
Email 75824 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
No Results