Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001548123
Ethics application status
Approved
Date submitted
22/10/2019
Date registered
11/11/2019
Date last updated
21/03/2022
Date data sharing statement initially provided
11/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Double NAC trial: Investigation of increased N-acetylcysteine dosing in patients treated for paracetamol overdose.
Scientific title
Double NAC trial: Investigation of increased N-acetylcysteine dosing in patients treated for paracetamol overdose.
Secondary ID [1] 297092 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record
No

Health condition
Health condition(s) or problem(s) studied:
paracetamol overdose 311103 0
Condition category
Condition code
Injuries and Accidents 309735 309735 0 0
Poisoning

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
N-acetylcysteine (NAC) given intravenously 200mg/kg over 4 hours, followed by 200mg/kg over 16 hours
Intervention code [1] 313363 0
Treatment: Drugs
Comparator / control treatment
N-acetylcysteine (NAC) given intravenously 200mg/kg over 4 hours, followed by 100mg/kg over 16 hours
Control group
Active

Outcomes
Primary outcome [1] 318696 0
The primary outcomes will be the rate of “hepatic injury” (defined to be alanine transaminase (ALT) doubling and peak ALT >100IU/L measured at 20 hrs after the commencement of NAC infusion) and need for further antidote. ALT is assessed by serum assay. This is a composite primary outcome
Timepoint [1] 318696 0
0 and 20 hours post initiation of NAC
Secondary outcome [1] 365751 0
These will include development of hepatotoxicity (defined as ALT >1000 IU/L). ALT measured by serum assay.
Timepoint [1] 365751 0
0,20 hours post initiation and every 12 hrs till ALT peaked and downtrending
Secondary outcome [2] 376328 0
Peak INR>2. Measured by blood test.
Timepoint [2] 376328 0
During hospital admission (up to 2 weeks)
Secondary outcome [3] 376329 0
Development of fulminant hepatic failure. Determined by bedside/clinical assessment.
Timepoint [3] 376329 0
During hospital admission (up to 2 weeks)
Secondary outcome [4] 376330 0
Mortality. Determined by Bedside assessment.
Timepoint [4] 376330 0
During hospital admission (anytime up to 4 weeks post admission)
Secondary outcome [5] 376331 0
Adverse reactions to N-acetylcysteine. These may include angioedema, rash, hypotension, vomiting, nausea, wheeze. Determined by clinical examination
Timepoint [5] 376331 0
Up to 20 hours post initiation of N-acetylcysteine.

Eligibility
Key inclusion criteria
Patients requiring NAC following single acute or staggered overdose with abnormal liver function tests on presentation (ALT>40 U/L), or paracetamol concentration more than double the nomogram treatment line, modified-release paracetamol paracetamol ingestions.
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria will be patients who are pregnant, intoxicated or sedated patients with co-ingested alcohol or sedating drugs. Single acute overdose patients who are at low risk - normal ALT (<40 IU/L) and paracetamol concentrations less than double the nomogram treatment line will be excluded. Patients with an ALT >40 IU/L on admission and documented preexisting liver disease will be excluded.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/02/2020
Actual
1/12/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
230
Accrual to date
75
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 12908 0
Dandenong Hospital - Dandenong
Recruitment hospital [2] 12909 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [3] 12910 0
Casey Hospital - Berwick
Recruitment hospital [4] 12911 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [5] 12912 0
Blacktown Hospital - Blacktown
Recruitment hospital [6] 12914 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 25385 0
3175 - Dandenong
Recruitment postcode(s) [2] 25386 0
3084 - Heidelberg
Recruitment postcode(s) [3] 25387 0
3806 - Berwick
Recruitment postcode(s) [4] 25388 0
3168 - Clayton
Recruitment postcode(s) [5] 25389 0
2148 - Blacktown
Recruitment postcode(s) [6] 25391 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 301659 0
Hospital
Name [1] 301659 0
Monash Health
Country [1] 301659 0
Australia
Primary sponsor type
Hospital
Name
Monash Health
Address
246 Clayton Road
Clayton
Victoria 3168
Country
Australia
Secondary sponsor category [1] 301372 0
None
Name [1] 301372 0
Address [1] 301372 0
Country [1] 301372 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302379 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 302379 0
246 Clayton Road
Clayton
Victoria 3168
Ethics committee country [1] 302379 0
Australia
Date submitted for ethics approval [1] 302379 0
16/01/2019
Approval date [1] 302379 0
15/03/2019
Ethics approval number [1] 302379 0

Summary
Brief summary
Paracetamol is one of the most common medications taken in overdose around the world. It is readily available and does not require a prescription to purchase. N-acetylcysteine (NAC) is the antidote used to treat patients at risk of developing liver toxicity secondary to the metabolites of paracetamol that accumulate following paracetamol overdose. The standard NAC treatment regimen lasts 20 to 21 hours and requires admission to hospital.
Patients who present to hospital and receive NAC for paracetamol overdose and have normal liver function and subsequently have a less than therapeutic paracetamol concentration and normal liver function with at least 12 hours of treatment with NAC are unlikely to go on to develop liver toxicity.
Conversely, patients who present late (greater than 8 hours post ingestion) to hospital, or with abnormal liver function, high paracetamol concentration and require NAC treatment, are likely to require a prolonged course of treatment and might develop liver failure.
We aim to increase the dose of NAC in this high risk group and examine whether this decreases degree of liver injury and hospital length of stay.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 90026 0
Dr Anselm Wong
Address 90026 0
Emergency Department
Austin Hospital
145 Studley Road
Heidelberg
Victoria 3084
Country 90026 0
Australia
Phone 90026 0
+61 3 94965000
Fax 90026 0
Email 90026 0
[email protected]
Contact person for public queries
Name 90027 0
Anselm Wong
Address 90027 0
Emergency Department
Austin Hospital
145 Studley Road
Heidelberg
Victoria 3084
Country 90027 0
Australia
Phone 90027 0
+61 3 94965000
Fax 90027 0
Email 90027 0
[email protected]
Contact person for scientific queries
Name 90028 0
Anselm Wong
Address 90028 0
Emergency Department
145 Austin Hospital
Studley Road
Heidelberg
Victoria 3084
Country 90028 0
Australia
Phone 90028 0
+61 3 94965000
Fax 90028 0
Email 90028 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
-


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.