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Trial registered on ANZCTR


Registration number
ACTRN12611000588998
Ethics application status
Approved
Date submitted
31/05/2011
Date registered
7/06/2011
Date last updated
21/01/2020
Date data sharing statement initially provided
21/01/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised controlled trial of antivenom for red-bellied black snake envenoming
Scientific title
A multicentre double-blind randomised placebo-controlled trial of early antivenom versus placebo in the treatment of red bellied black snake envenoming
Secondary ID [1] 262282 0
Nil
Universal Trial Number (UTN)
Trial acronym
RBBS RCT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Red-bellied black snake envenoming 267984 0
Condition category
Condition code
Injuries and Accidents 268116 268116 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study tests two treatments in two arms:

1. 1 vial of tiger snake antivenom (3000 Units)
2. A matched volume of 50% glucose (Placebo)

Antivenom = 1 vial of Tiger snake antivenom (3000 Units; CSL Ltd) given intravenously diluted in 200mL of normal saline over 20 minutes.
Intervention code [1] 266673 0
Treatment: Drugs
Comparator / control treatment
Antivenom placebo will be an equally matched volume of 50% glucose in an identical vial to the tiger snake antivenom vial (purchased from CSL empty)
Control group
Placebo

Outcomes
Primary outcome [1] 266865 0
The proportion of patients with myotoxicity defined as a peak creatine kinase greater than 1000U/L. Creatine kinase is a standard biochemistry assay that will be done by the treating hospital (as part of standard care).
Timepoint [1] 266865 0
24 hours or the time after the first creatine kinase greater than 1000U/L
Secondary outcome [1] 276522 0
Disappearance of all non-specific systemic symptoms as assessed by history (interview) from the patient by the treating doctor.
Timepoint [1] 276522 0
1 hour after antivenom
Secondary outcome [2] 276523 0
Normalisation of the activated partial thromboplastin time which will be measured by the treating hospital laboratory. This is a standard coagulation test.
Timepoint [2] 276523 0
1 hour after antivenom
Secondary outcome [3] 276524 0
Anosmia based on patient interview
Timepoint [3] 276524 0
7 days after antivenom
Secondary outcome [4] 276525 0
Area under the creatine kinase curve
Timepoint [4] 276525 0
7 days after the snake bite
Secondary outcome [5] 276526 0
Absence of free circulating venom by enzyme immunoassay
Timepoint [5] 276526 0
1 hour after antivenom administration
Secondary outcome [6] 276527 0
Early adverse reactions to antivenom as defined by the Brown grading for allergic reactions.

Brown, S.G., Clinical features and severity grading of anaphylaxis. Journal of Allergy and Clinical Immunology, 2004. 114(2): p. 371-376
Timepoint [6] 276527 0
Within 4 hours of antivenom
Secondary outcome [7] 328742 0
Serum sickness defined as three or more of the following characteristic clinical features 7 to 21 days after antivenom administration - fever, erythematous rash, urticaria (hives), myalgia/arthralgia, headache, malaise and nausea/vomiting, and confirmation by an experienced Toxicologist.
Timepoint [7] 328742 0
7 days to 21 days after antivenom administration

Eligibility
Key inclusion criteria
1. Definite bite by a red-bellied black snake:

a.Expert identification of the snake or snake brought in and identified by a photograph sent to the investigators; OR
b.Characteristic description of a RBBS (black snake with red sides and cream/yellow ventral surface) AND detection of black snake (or black snake/tiger snake) on a snake venom detection kit.

2. Early evidence of envenoming (any of):
a. Non-specific systemic effects including two of nausea/vomiting, headache, abdominal pain, diarrhoea
b. Anticoagulant coagulopathy defined as an activated partial thromboplastin time above the normal range for the local laboratory
c. Significant local tissue injury with swelling, bruising and erythema >5 cm diameter
Minimum age
2 Years
Maximum age
99 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Nil

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)
Enrolment will be triggered by a variety of complementary methods proven to be highly effective with the Australian snakebite project. These include regular staff education regarding trial processes, emergency department triage triggers and signs on antivenom containers in drug refrigerators. Enrolment will require contacting the 1800 676 944 phone number diverted to one of the chief investigators or research data manager. The on-call investigator/data manager will keep a list of all study packs at each hospital. Brief demographic and clinical data will be faxed, and after informed consent is confirmed, the randomisation will be done by a secure online website. The website will contain a database of all treatment packs at each hospital and provide the study code for the treatment pack that is required. The treating team will simply find the treatment pack with the corresponding study code.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomisation will be used with random block-sizes which will then be organised into packs of 4 treatments for each site.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis

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
Recruitment hospital [1] 3097 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [2] 3099 0
John Hunter Hospital Royal Newcastle Centre - New Lambton
Recruitment hospital [3] 3102 0
Manning Rural Referral Hospital (Taree) - Taree
Recruitment hospital [4] 3103 0
Belmont Hospital - Belmont
Recruitment postcode(s) [1] 8850 0
2298 - Waratah
Recruitment postcode(s) [2] 8851 0
2305 - New Lambton Heights
Recruitment postcode(s) [3] 8853 0
2430 - Taree
Recruitment postcode(s) [4] 8854 0
2280 - Belmont

Funding & Sponsors
Funding source category [1] 267166 0
Government body
Name [1] 267166 0
NHMRC
Address [1] 267166 0
Level 1
16 Marcus Clarke Street
Canberra ACT 2601
Country [1] 267166 0
Australia
Primary sponsor type
Individual
Name
Geoff Isbister
Address
Department of Clinical Toxicology and Pharmacology
Calvary Mater Newcastle
Edith St
Waratah NSW 2298
Country
Australia
Secondary sponsor category [1] 266240 0
University
Name [1] 266240 0
University of Newcastle
Address [1] 266240 0
Clinical Toxicology Research Group, The University of Newcastle,
Level 5 New Med Building, Calvary Mater Newcastle,
Edith Street WARATAH NSW 2298.
Country [1] 266240 0
Australia
Other collaborator category [1] 252035 0
Individual
Name [1] 252035 0
Nick Buckley
Address [1] 252035 0
Medical Professorial Unit
Faculty of Medicine
UNSW
Sydney NSW 2052
Country [1] 252035 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 269155 0
Hunter New England Area Health Service Human Research Ethics Committee
Ethics committee address [1] 269155 0
Hunter New England Research and Governance Unit
Locked Bag 1
New Lambton NSW 2305
Ethics committee country [1] 269155 0
Australia
Date submitted for ethics approval [1] 269155 0
Approval date [1] 269155 0
17/03/2011
Ethics approval number [1] 269155 0
10/12/15/3.04

Summary
Brief summary
Muscle damage can result from snake bite which is irreversible and there is no specific treatment for except
antivenom. Redbellied black snake bite provides a unique opportunity to study antivenom use in muscle damage in snake bite because this snake occurs across large population areas of NSW and Queensland. The study will
determine if antivenom is effective and safe in red bellied black snake bite and whether it is therefore useful for other important snakes that cause muscle damage worldwide.
Trial website
http://www.newcastle.edu.au/research-and-innovation/centre/health-medicine/clinical-toxicology
Trial related presentations / publications
Churchman A, O’Leary MA, Buckley NA, Page CP, Tankel A, Gavaghan C, Holdgate A, Brown SGA, Isbister GK Clinical effects of red-bellied black snake (Pseudechis porphyriacus) envenoming and correlation with venom concentrations: Australian snakebite project (ASP-11). Med J Aust. 2010 Dec 6;193(11-12):696-700
Public notes

Contacts
Principal investigator
Name 32679 0
Prof Geoff Isbister
Address 32679 0
Clinical Toxicology Research Group, The University of Newcastle
Level 5 New Med Building, Calvary Mater Newcastle,
Edith Street, Waratah NSW 2298.
Country 32679 0
Australia
Phone 32679 0
+61 2 49211211
Fax 32679 0
Email 32679 0
geoff.isbister@gmail.com
Contact person for public queries
Name 15926 0
Prof Geoff Isbister
Address 15926 0
Clinical Toxicology Research Group, The University of Newcastle
Level 5 New Med Building, Calvary Mater Newcastle,
Edith Street, Waratah NSW 2298.
Country 15926 0
Australia
Phone 15926 0
+61 438466471
Fax 15926 0
Email 15926 0
geoff.isbister@gmail.com
Contact person for scientific queries
Name 6854 0
Prof Geoff Isbister
Address 6854 0
Clinical Toxicology Research Group, The University of Newcastle
Level 5 New Med Building, Calvary Mater Newcastle,
Edith Street, Waratah NSW 2298.
Country 6854 0
Australia
Phone 6854 0
+61 438466471
Fax 6854 0
Email 6854 0
geoff.isbister@gmail.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Due to duration of study it will be too difficult to contact patients to get approval to share data
What supporting documents are/will be available?
No other documents available
Summary results
No Results