Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12607000620426
Ethics application status
Approved
Date submitted
9/10/2007
Date registered
3/12/2007
Date last updated
12/08/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomised Controlled Trial Of Factor Replacement Therapy In Snake Bite Coagulopathy
Scientific title
A Randomised Controlled Trial Of Fresh Frozen Plasma (FFP) for Venom Induced Consumption Coagulopathy in Australian snakebite
Secondary ID [1] 281144 0
Nil
Universal Trial Number (UTN)
Trial acronym
ASP - FFP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Venom Induced Consumption Coagulopathy (VICC) from Australian snake envenoming 2437 0
Condition category
Condition code
Injuries and Accidents 2540 2540 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Fresh frozen plasma (FFP), 6 units administered within 4 hours of antivenom treatment
Intervention code [1] 2164 0
Treatment: Drugs
Comparator / control treatment
No treatment defined as no administration of FFP or other clotting factors within 4 hours of antivenom.
Control group
Placebo

Outcomes
Primary outcome [1] 3444 0
The proportion of patients with a return of coagulation function defined by an International Normalised Ratio (INR) < 2.0 (or PT < 24 seconds where INR is not performed)
Timepoint [1] 3444 0
Six hours after antivenom treatment commenced
Secondary outcome [1] 5729 0
Pattern of improvement in clotting function and increase in clotting factors: fibrinogen, prothrombin, factor V and factor VIII. Blood samples will be taken prior to antivenom, 3,6 12 and 24 hours after antivenom.
Timepoint [1] 5729 0
investigation of improvement of multiple clotting factors over time.
Secondary outcome [2] 5730 0
The number of hours after commencing antivenom until discharge from hospital (hours).
Timepoint [2] 5730 0
Time from commencing antivenom until discharge from hospital (hours)
Secondary outcome [3] 5731 0
Major bleeding, as defined by the International Society on Thrombosis and Haemostasis: Fatal bleeding; Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome; Bleeding causing a fall in haemoglobin level of 20 g/L or more, or leading to transfusion of two or more units of whole blood or red cells.
Timepoint [3] 5731 0
While in hospital
Secondary outcome [4] 5732 0
Death
Timepoint [4] 5732 0
While in hospital
Secondary outcome [5] 5733 0
Adverse reactions
Timepoint [5] 5733 0
While in hospital

Eligibility
Key inclusion criteria
1. Venom induced consumption coagulopathy defined as: an INR (or PT) or aPTT more than twice the normal upper limit AND a positive D-dimer;
2. Antivenom administered for the appropriate snake: brown, tiger or taipan;
3. 6 units of FFP is available and can be administered to the patient within 4 hours of commencing antivenom, either at the presenting hospital or on arrival at a regional hospital nearby if transfer can be initiated in time;
Minimum age
5 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Known adverse reactions to blood products

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)
Patients will be enrolled from cases of snake envenoming identified to the principal investigators from around Australia. Cases that meet the inclusion criteria will be randomised centrally in a 2:1 schedule to either receive fresh frozen plasma or no treatment following the administration of antivenom. Blinded allocation will be maintained by the investigators and research assistants by using the PDAs to provide the random allocation. A Microsoft Access database form (reduced version for PDAs) will be used to implement this. The investigator must first enter the patient’s baseline characteristics and non-identifiable information which will allow recruitment. If the patient meets criteria to be randomised for FFP treatment then further information will need to be entered (coagulation studies results, consent obtained and FFP available). Once this has been supplied the program will then randomise and allocate the patient for the study. This will mean that the investigator and treating doctor will not be aware of the allocation until the patient is eligible for recruitment and they have consented.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated random sequence using Microsoft Excel.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
2:1 randomisation because of the chance that patients randomised to fresh frozen plasma may not actually be given fresh frozen plasma within the time frame for logistic reasons.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/01/2008
Actual
1/03/2008
Date of last participant enrolment
Anticipated
Actual
30/06/2012
Date of last data collection
Anticipated
Actual
30/06/2012
Sample size
Target
102
Accrual to date
Final
65
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA

Funding & Sponsors
Funding source category [1] 2687 0
Government body
Name [1] 2687 0
NHRMC Project Grant
Country [1] 2687 0
Australia
Primary sponsor type
Individual
Name
Geoffrey Isbister
Address
Calvary Mater Newcastle
Edith St
Waratah NSW 2298
Country
Australia
Secondary sponsor category [1] 2431 0
Individual
Name [1] 2431 0
Simon Brown
Address [1] 2431 0
Emergency Research Unit
Fremantle Hospital
Fremantle
Country [1] 2431 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 4608 0
Ethics committee address [1] 4608 0
Ethics committee country [1] 4608 0
Date submitted for ethics approval [1] 4608 0
01/11/2007
Approval date [1] 4608 0
Ethics approval number [1] 4608 0
Ethics committee name [2] 295728 0
Hunter and New England HREC
Ethics committee address [2] 295728 0
Newcastle
Ethics committee country [2] 295728 0
Australia
Date submitted for ethics approval [2] 295728 0
30/10/2007
Approval date [2] 295728 0
29/11/2007
Ethics approval number [2] 295728 0
07/11/21/3.06

Summary
Brief summary
The study aims to determine if the early administration of clotting factors (ie. FFP) to patients with a procoagulant coagulopathy following snake envenoing will speed the patient recovery of clotting function. A secondary aim to confirm that smaller doses of antivenom are sufficient for the treatment of coagulopathy.
Trial website
Trial related presentations / publications
Isbister GK, Buckley NA, Page CB, et al. A randomized controlled trial of fresh frozen plasma for treating venom-induced consumption coagulopathy in cases of Australian snakebite (ASP-18). J Thromb Haemost 2013; 11(7): 1310-8
Public notes

Contacts
Principal investigator
Name 28101 0
Prof Geoffrey Isbister
Address 28101 0
Calvary Mater Newcastle
Waratah NSW 2298
Country 28101 0
Australia
Phone 28101 0
0438466471
Fax 28101 0
Email 28101 0
[email protected]
Contact person for public queries
Name 11258 0
Prof Geoff Isbister
Address 11258 0
Calvary Mater Newcastle
Edith St
Waratah NSW 2298
Country 11258 0
Australia
Phone 11258 0
02 49211211
Fax 11258 0
02 94754893
Email 11258 0
[email protected]
Contact person for scientific queries
Name 2186 0
Prof Geoff Isbister
Address 2186 0
Calvary Mater Newcastle
Edith St
Waratah NSW 2298
Country 2186 0
Australia
Phone 2186 0
02 49211211
Fax 2186 0
02 94754893
Email 2186 0
[email protected]

No information has been provided regarding IPD availability


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
SourceTitleYear of PublicationDOI
Dimensions AIA randomized controlled trial of fresh frozen plasma for treating venom-induced consumption coagulopathy in cases of Australian snakebite (ASP-18)2013https://doi.org/10.1111/jth.12218
N.B. These documents automatically identified may not have been verified by the study sponsor.