Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001549112
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
The NACSTOP 2 trial: Investigation of the early cessation of N-acetylcysteine in patients following paracetamol overdose.
Scientific title
The NACSTOP 2 trial: Investigation of the early cessation of N-acetylcysteine in patients following paracetamol overdose.
Secondary ID [1] 297079 0
Nil known
Universal Trial Number (UTN)
Trial acronym
NACSTOP 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
paracetamol overdose 311088 0
Condition category
Condition code
Injuries and Accidents 309720 309720 0 0
Poisoning

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
N-acetylcysteine (NAC) given intravenously as 200mg/kg over 4 hours (infusion 1), then 100 mg/kg over 16 hour infusion rate (infusion 2) ie. at least half will be given e.g. 50mg/kg over 8 hours. Depending on 12 hour post initiation blood tests, infusion 2 may be ceased after at least 8 hours of infusion. ie . 12 hour protocol
Intervention code [1] 313355 0
Treatment: Drugs
Comparator / control treatment
NAC given intravenously as 200mg/kg over 4 hours (infusion 1), then 100 mg/kg over 16 hours (infusion 2) ie. 20 hour infusion protocol.
Control group
Active

Outcomes
Primary outcome [1] 318687 0
Primary outcome: The primary outcome will be the absolute difference between alanine transaminase (ALT) on admission and after 20 hours of NAC. This will be assessed by serum assay.
Timepoint [1] 318687 0
20 hours post initiation of NAC
Secondary outcome [1] 365732 0
Hepatic injury” (defined to be ALT doubling and peak ALT >100IU/L measured at 20 hrs after the commencement of NAC infusion) and need for further antidote (determine from hospital records-continued if ALT >40IU/L or paracetamol>10mg/L). This is a composite outcome. ALT is measured by serum assay.
Timepoint [1] 365732 0
20 hours post initiation of NAC.
Secondary outcome [2] 376333 0
hepatotoxicity (ALT >1000). Assessed by serum assay
Timepoint [2] 376333 0
during hospital admission (up to 2 weeks)
Secondary outcome [3] 376334 0
Peak INR>2. Serum assay
Timepoint [3] 376334 0
during hospital admission (up to 2 weeks)
Secondary outcome [4] 376335 0
Adverse reactions to NAC (nausea, vomiting, rash, hypotension, wheeze, angioedema). Assessed by bedside exam.
Timepoint [4] 376335 0
up to 20 hours post initiation NAC

Eligibility
Key inclusion criteria
Inclusion criteria will be patients requiring NAC following paracetamol overdose presenting with single paracetamol and staggered ingestions with normal liver function tests (ALT <40 IU/L) and paracetamol concentration < 132 micromol/L (20 mg/L) after 12 hours of NAC.
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 presenting with a history of supratherapeutic ingestion of paracetamol (>10grams over 24 hours, >6 grams/day over 48 hrs), intoxicated or sedated patients with co-ingested alcohol or sedating drugs, modified release paracetamol ingestion, patients with preexisting liver disease evidenced by abnormal liver function tests, and pregnancy. If the ALT is >40 IU/L or paracetamol concentration > 132 micromol/L (20 mg/L) after 12 hours of NAC, they will receive the full course of NAC and be excluded from the study.

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
200
Accrual to date
100
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 12899 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 12900 0
Dandenong Hospital - Dandenong
Recruitment hospital [3] 12901 0
Casey Hospital - Berwick
Recruitment hospital [4] 12902 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [5] 12903 0
Westmead Hospital - Westmead
Recruitment hospital [6] 12904 0
Blacktown Hospital - Blacktown
Recruitment postcode(s) [1] 25376 0
3084 - Heidelberg
Recruitment postcode(s) [2] 25377 0
3175 - Dandenong
Recruitment postcode(s) [3] 25378 0
3806 - Berwick
Recruitment postcode(s) [4] 25379 0
3168 - Clayton
Recruitment postcode(s) [5] 25380 0
2145 - Westmead
Recruitment postcode(s) [6] 25381 0
2148 - Blacktown

Funding & Sponsors
Funding source category [1] 301645 0
Hospital
Name [1] 301645 0
Monash Health
Country [1] 301645 0
Australia
Primary sponsor type
Hospital
Name
Monash Health
Address
246 Clayton Road
Clayton
Victoria 3168
Country
Australia
Secondary sponsor category [1] 301359 0
None
Name [1] 301359 0
Address [1] 301359 0
Country [1] 301359 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302367 0
Monash Health Research Ethics Committee
Ethics committee address [1] 302367 0
Monash Health
246 Clayton Road
Clayton
Victoria 3168
Ethics committee country [1] 302367 0
Australia
Date submitted for ethics approval [1] 302367 0
31/01/2019
Approval date [1] 302367 0
15/04/2019
Ethics approval number [1] 302367 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.
All study participants will be required to stay in hospital for the usual 20 hours (the time for a standard NAC infusion as per the current treatment guidelines) and will have liver function tests measured at this time.
This trial aims to determine that a shorter treatment regimen (12 hrs) for paracetamol overdose is safe.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89982 0
Dr Anselm Wong
Address 89982 0
Emergency Department
145 Studley Road
Austin Hospital
Heidelberg Victoria 3084
Country 89982 0
Australia
Phone 89982 0
+61 3 94964509
Fax 89982 0
Email 89982 0
[email protected]
Contact person for public queries
Name 89983 0
Dr Anselm Wong
Address 89983 0
Emergency Department
145 Studley Road
Austin Hospital
Heidelberg Victoria 3084
Country 89983 0
Australia
Phone 89983 0
+61 3 94964509
Fax 89983 0
Email 89983 0
[email protected]
Contact person for scientific queries
Name 89984 0
Dr Anselm Wong
Address 89984 0
Emergency Department
145 Studley Road
Austin Hospital
Heidelberg Victoria 3084
Country 89984 0
Australia
Phone 89984 0
+61 3 94964509
Fax 89984 0
Email 89984 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.