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Trial registered on ANZCTR


Registration number
ACTRN12608000611325
Ethics application status
Approved
Date submitted
22/09/2008
Date registered
5/12/2008
Date last updated
11/08/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Russell’s Viper Coagulopathy Fresh Frozen Plasma Study
Scientific title
Randomised controlled trial of fresh frozen plasma to speed the recovering of venom induced consumption coagulopathy in patients with Russell's Viper envenoming in Sri Lanka.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Snake Envenoming 3734 0
Condition category
Condition code
Other 3904 3904 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above
Injuries and Accidents 3905 3905 0 0
Other injuries and accidents
Blood 3906 3906 0 0
Clotting disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intravenous fresh frozen plasma, 10mL/kg up to 4 units, within 4 hours of the commencement of first antivenom therapy. Antivenom treatment will be according to the current recommendation in Sril Lanka of 20 vials of Indian polyvalent antisnake venom (VINS or Haffkine) administered over 1 hour intravenously.
Intervention code [1] 3448 0
Treatment: Other
Comparator / control treatment
Intravenous normal saline, 10mL/kg, within 4 hours of the commencement of first antivenom therapy. Antivenom treatment will be according to the current recommendation in Sril Lanka of 20 vials of Indian polyvalent antisnake venom (VINS or Haffkine) administered over 1 hour intravenously.
Control group
Placebo

Outcomes
Primary outcome [1] 4805 0
The proportion of patients with a significant return of coagulation function defined by an International Normalised Ratio (INR) < 2.0 (or prothrombin time (PT) < 24 seconds where INR was not performed)
Timepoint [1] 4805 0
6 hours after antivenom treatment is commenced
Primary outcome [2] 4806 0
The frequency of major adverse outcomes in the fresh frozen plasma (FFP) arm compared to the non-FFP arm. Major adverse outcomes will be defined as:
1. Severe anaphylaxis according to the Brown Criteria (this will be recorded and no attempt will be made to attribute to antivenom or FFP)
2. Transfusion-Related Acute Lung Injury (TRALI) according to the following criteria:
(i) Acute onset within 6 hours of the administration of FFP or antivenom
(ii) Hypoxaemia: pO2 < 90% or other evidence of hypoxaemia if oxygen saturation not available.
(iii) Bilateral infiltrates on a frontal chest X-ray (if no X-ray available then this criteria will be waived)
(iv) No evidence of circulatory overload/left atrial hypertension
(v) No preceding acute lung injury
(vi) No temporal relationship to an alternative risk factor for acute lung injury
3. Death occurring prior to discharge from hospital.
Timepoint [2] 4806 0
Any time during the study which will continue until the patient is discharged from hospital. All patients will be seen by study investigators every 8 hours during the study.
Secondary outcome [1] 8110 0
Improvement in clotting function and increase in clotting factors measured by blood analyis at 3 hours and 6 hours:
a. Fibrinogen
b. Factor V
c. Factor VIII
d. Prothrombin
e. Factor X
Timepoint [1] 8110 0
At 3 hours and 6 hours
Secondary outcome [2] 8111 0
Time from commencing antivenom until discharge from hospital (hours)
Timepoint [2] 8111 0
Discharge from hospital
Secondary outcome [3] 8112 0
Major bleeding, as defined by the International Society on Thrombosis and Haemostasis5:
(i) Fatal bleeding,
(ii) Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome,
(iii) 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] 8112 0
Bleeding will be assessed by clinical examination when the patient is seen daily on ward rounds and every 8 hours by the study team up until the time of discharge from hospital.

Eligibility
Key inclusion criteria
a) Venom induced consumption coagulopathy defined as: whole blood clotting time (WBCT) > 20 minutes
b) No known adverse reactions to blood products
c) Antivenom is or will be administered to treat the patient
d) Up to a maximum of 4 units of FFP is available and can be commenced to the patient within 4 hours of commencing antivenom.
Minimum age
14 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a) Age < 14 year
b) Pregnancy

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)
Once a snake envenoming case is identified by the research assistants or investigators the patient will be assessed for suitability for inclusion in the study. If they meet the inclusion criteria they will be consented to the study. The patient will be randomly allocated to receive either 10mL/kg of FFP (up to a maximum of 4 units) over 60 minutes or 10mL/kg of normal saline over 60 minutes.

Allocation will be done by the research team contacting an "off-site" person who will provide the randomisation to them over the phone.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
An adaptive biased coin randomisation schedule will be used. This will be done by having simple randomisation on a study hand held computer and then uploading recruited cases with baseline details and treatment allocation to a central database. The central database will be monitored by an independent member of the South Asian Clinical Toxicology Research Collaboration who will not be involved in patient treatment, random allocation or data collection. If the randomisation becomes unbalanced (ie. > 50% or <50% in the FFP arm) then the probability will be biased to correct the imbalance (ie. 0.6/0.4 instead of 0.5/0.5) by implementing a biased coin randomisation to the PDAs. In addition to balancing FFP across all patients, there will be additional minimisation protocol based on the time of antivenom after the bite with patients being put into 3 groups: AVS < 4hrs from bite; AVS between 4 and 8 hours after the bite; and AVS > 8 hours after the bite.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Date of first participant enrolment
Anticipated
1/10/2008
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
700
Accrual to date
Final
Recruitment outside Australia
Country [1] 1230 0
Sri Lanka
State/province [1] 1230 0
Central and North Central

Funding & Sponsors
Funding source category [1] 3913 0
Self funded/Unfunded
Name [1] 3913 0
Country [1] 3913 0
Primary sponsor type
Individual
Name
Geoff Isbister
Address
Calvary Mater Newcastle Hospital
Edith St
Waratah NSW 2298
Country
Australia
Secondary sponsor category [1] 3510 0
Individual
Name [1] 3510 0
Indika Gawarammana
Address [1] 3510 0
Dept of Clinical Medicine
Faculty of Medicine
University Dr
University of Peradeniya
Peradeniya
Country [1] 3510 0
Sri Lanka

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5973 0
Committee on Research and Ethical Review
Ethics committee address [1] 5973 0
Ethics committee country [1] 5973 0
Sri Lanka
Date submitted for ethics approval [1] 5973 0
Approval date [1] 5973 0
07/04/2008
Ethics approval number [1] 5973 0
2008/EC/26

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28965 0
Prof Geoffrey Isbister
Address 28965 0
Calvary Mater Newcastle
Waratah NSW 2298
Country 28965 0
Australia
Phone 28965 0
0438466471
Fax 28965 0
Email 28965 0
[email protected]
Contact person for public queries
Name 12122 0
Indika Gawarammana
Address 12122 0
Dept of Clinical Medicine
Faculty of Medicine
University of Peradeniya
University Dr
Peradeniya
Country 12122 0
Sri Lanka
Phone 12122 0
+94814479822
Fax 12122 0
Email 12122 0
[email protected]
Contact person for scientific queries
Name 3050 0
Geoff Isbister
Address 3050 0
Calvary Mater Newcastle Hospital
Edith St
Waratah NSW 2298
Country 3050 0
Australia
Phone 3050 0
+61 2 49211211
Fax 3050 0
Email 3050 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

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