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Trial registered on ANZCTR


Registration number
ACTRN12622000763741
Ethics application status
Approved
Date submitted
17/05/2022
Date registered
27/05/2022
Date last updated
19/12/2022
Date data sharing statement initially provided
27/05/2022
Date results information initially provided
19/12/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Pre-hospital Freeze-Dried Plasma for critical bleeding after trauma: A pilot trial
Scientific title
Pre-hospital Freeze-Dried Plasma for critical bleeding after trauma among adult patients receiving blood transfusion: A pilot trial
Secondary ID [1] 307149 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Trauma 326344 0
Bleeding 326345 0
Acute traumatic coagulopathy 326346 0
Condition category
Condition code
Emergency medicine 323649 323649 0 0
Resuscitation
Blood 323650 323650 0 0
Clotting disorders
Injuries and Accidents 323651 323651 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Two units of freeze-dried plasma (total reconstituted volume of 400mL) will be infused intravenously after transfusion of the first unit of red cell concentrate. The infusion will be delivered as fast as possible, as tolerated by the intravenous access.
The infusion of freeze-dried plasma, once commenced, will be continued in hospital until completion of the entire intervention dose.
Intervention code [1] 323601 0
Treatment: Other
Comparator / control treatment
Among patients allocated to the standard care arm, management will be as dictated by Ambulance Victoria clinical practice guidelines. For the eligible population, this is usually red cell concentrates, up to 4 units, calcium gluconate and additional crystalloid fluids if indicated. Helicopter Emergency Medical services in Victoria carry 4 units of red cell concentrates, that would be the maximum transfusion volume..
Control group
Active

Outcomes
Primary outcome [1] 331393 0
The proportion of eligible patients (meeting all the inclusion criteria and none of the exclusion criteria) who are randomised and complete the intervention. After completion of enrolment, this will be determined by a retrospective review of Ambulance Victoria medical records to identify all patients who had received red cell concentrates during the study period.
Timepoint [1] 331393 0
Cumulative data will be assessed at the conclusion of the study enrolment period.
Secondary outcome [1] 409715 0
Proportion of randomised patients who complete the intervention. This data will be prospectively collected on arrival of the patient to hospital from Ambulance Victoria medical records.
Timepoint [1] 409715 0
Within 1st hour of hospital presentation
Secondary outcome [2] 409716 0
Death
Timepoint [2] 409716 0
Within 24h of trauma
Secondary outcome [3] 409717 0
Death
Timepoint [3] 409717 0
At hospital discharge
Secondary outcome [4] 409718 0
Hospital length of stay determined by a review of patient medical records.
Timepoint [4] 409718 0
At time of hospital discharge.
Secondary outcome [5] 409719 0
ICU length of stay determined by a review of patient medical records.
Timepoint [5] 409719 0
At time of ICU discharge.
Secondary outcome [6] 409721 0
Total blood product use, determined after a review of Ambulance and hospital medical records.
Timepoint [6] 409721 0
24h of hospital admission
Secondary outcome [7] 409722 0
The number and type of adverse events, serious adverse events and Suspected Unexpected Serious Adverse Reactions (SUSARs) will be recorded as a composite endpoint.
Serious Adverse Events (SAE) are defined in accordance with the Note for Guidance on Clinical Safety Data Management: Definitions and Standards for Expedited Reporting (CPMP/ICH/377/95) (July 2000) as any untoward medical occurrence that:
• Results in death
• Is life-threatening
• Requires inpatient hospitalisation or prolongation of existing hospitalisation
• Results in persistent or significant disability/incapacity
• Is a congenital anomaly/birth defect
• Is an important medical event that may require intervention to prevent one of the previously listed outcomes.

A suspected unexpected serious adverse reaction (SUSAR) is an SAE that is not expected based on information that is currently available. Given the safety profile of Lyoplas N-w is well known, we do not anticipate many, if any, SUSARs.

SAEs and SUSARs will be reported to the ethics committee and data collected within 24 hours of identification. Adverse events already defined and reported as study outcomes (mortality, vascular occlusive events) will not be labelled and reported a second time as serious adverse events.

This data will be extracted from Ambulance Victoria and hospital medical records.
Timepoint [7] 409722 0
Hospital discharge
Secondary outcome [8] 409906 0
First international Normalised Ratio (INR) on arrival to hospital
Timepoint [8] 409906 0
Collected prospectively from hospital medical records on arrival to hospital
Secondary outcome [9] 409907 0
First Activated Partial Prothrombin Time (aPTT) on arrival to hospital
Timepoint [9] 409907 0
Collected prospectively from hospital medical records on arrival to hospital.
Secondary outcome [10] 409908 0
First platelet count on arrival to hospital.
Timepoint [10] 409908 0
Collected prospectively from hospital medical records on arrival to hospital.
Secondary outcome [11] 409909 0
First fibrinogen on arrival to hospital.
Timepoint [11] 409909 0
Collected prospectively from hospital medical records on arrival to hospital.

Eligibility
Key inclusion criteria
1. Adult patients (age greater than or equal to 18 years);
2. Injured through any mechanism;
3. Patients to be transported to a participating trauma centre (The Alfred).
4. Receiving any pre-hospital red cells as per Ambulance Victoria AAV Clinical Practice Guidelines
o The transfusion of red cells by HEMS paramedics was implemented in Victoria in April 2011. Primary emergency indication for the administration of red cells is evidence of shock (hypotension and/or tachycardia) following trauma.
5. Able to receive two units of pre-hospital freeze-dried plasma
Minimum age
18 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Extremes of age (>90 years or <18 years)
2. No intravenous access
3. Known pregnancy
4. Palliative care

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)
Trial packs will be consecutively numbered opaque packs with a tamper proof seal.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random permuted blocks with a Block size of 4.
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
Sample size of this feasibility trial was derived from the eligible population likely to be available during the study period and allowed budget. We aim to recruit 20 patients in this pilot trial, with 10 patients to be randomised to the intervention arm and 10 patients to the standard care arm.

The primary outcome of feasibility will be reported using proportions. A flow chart of all eligible patients, continuing to those that were assessed, randomised and those that completed the intervention will be presented. Proportions will be presented with 95% confidence intervals. For limited analysis of efficacy, all analyses will be undertaken on an intention-to-treat basis. It is unlikely that there will be crossover between the two arms, although it is likely that some patients will die prior to completion of the intervention. We expect to be able to capture data on the primary outcome of death without any missing data. However, in the unlikely event a subject’s survival status cannot be determined, the national registry of Births and Deaths will be interrogated. The proportion of mortality within arm will be computed and summarised using Relative Risk and reported with 95% confidence intervals. A p-value of <0.05 will be defined to be statistically significant. Given the small sample size, it is possible that despite randomisation, the two arms will not be balanced. Stata v 15.1 (Statacorp, College Station, TX) will be used for all analyses.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
30/05/2022
Actual
15/06/2022
Date of last participant enrolment
Anticipated
30/10/2022
Actual
31/10/2022
Date of last data collection
Anticipated
30/11/2022
Actual
1/12/2022
Sample size
Target
20
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 22386 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 37550 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 311452 0
Government body
Name [1] 311452 0
National Blood Authority
Country [1] 311452 0
Australia
Primary sponsor type
Hospital
Name
The Alfred
Address
55 Commercial Rd
Melbourne VIC 3004
Country
Australia
Secondary sponsor category [1] 312848 0
None
Name [1] 312848 0
Address [1] 312848 0
Country [1] 312848 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310924 0
Alfred Hospital Human Research and Ethics Committee
Ethics committee address [1] 310924 0
55 Commercial Rd
Melbourne VIC 3004
Ethics committee country [1] 310924 0
Australia
Date submitted for ethics approval [1] 310924 0
19/03/2021
Approval date [1] 310924 0
27/05/2021
Ethics approval number [1] 310924 0
224/21

Summary
Brief summary
This is a pilot feasibility trial of freeze-dried plasma vs standard therapy for patients with haemorrhagic shock receiving pre-hospital blood (Population). This will be an open label, randomised controlled trial.
The Intervention will be freeze-dried plasma, obtained for the trial from the German Red Cross (LyoPlas N-w).
The Comparator will be standard care, which in the Australian context is no plasma or other clotting factor replacement.
The primary Outcome will be feasibility of implementation, measured by the proportion of randomised patients who complete the intervention. Secondary outcomes, assessed for possible use as primary outcomes in any subsequent definitive trial, will include mortality at 24 hours and at hospital discharge, coagulation status on arrival to hospital, and total blood product use within 24 hours of hospital arrival.
Trial website
Trial related presentations / publications
Public notes
List of investigators:
Prof. Biswadev Mitra
Prof. Stephen Bernard
Prof. Michael Reade
Prof. Erica Wood
A/Prof. Zoe McQuilten
Prof. Russell Gruen
Prof. Marc Maegele
Prof. Karen Smith
A/Prof. Michael Stephenson
Mr. Anthony De Wit
Mr. Ben Meadley
Mr. Toby St. Clair
Dr. David Anderson
Prof. Mark Fitzgerald
Miss Olivia Bradley

Contacts
Principal investigator
Name 119366 0
Prof Biswadev Mitra
Address 119366 0
Biswadev Mitra
National Trauma Research Institute
Level 4, 89 Commercial Rd
Melbourne VIC 3004
Country 119366 0
Australia
Phone 119366 0
+61 3 9076 2782
Fax 119366 0
+61 3 9076 2699
Email 119366 0
biswadev.mitra@monash.edu
Contact person for public queries
Name 119367 0
Prof Biswadev Mitra
Address 119367 0
Biswadev Mitra
National Trauma Research Institute
Level 4, 89 Commercial Rd
Melbourne VIC 3004
Country 119367 0
Australia
Phone 119367 0
+61 3 9076 2782
Fax 119367 0
+61 3 9076 2699
Email 119367 0
biswadev.mitra@monash.edu
Contact person for scientific queries
Name 119368 0
Prof Biswadev Mitra
Address 119368 0
Biswadev Mitra
National Trauma Research Institute
Level 4, 89 Commercial Rd
Melbourne VIC 3004
Country 119368 0
Australia
Phone 119368 0
+61 3 9076 2782
Fax 119368 0
+61 3 9076 2699
Email 119368 0
biswadev.mitra@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Small pilot study; potentially re-identifiable patients


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
EmbasePre-hospital freeze-dried plasma for critical bleeding after trauma: A pilot randomized controlled trial.2023https://dx.doi.org/10.1111/acem.14745
N.B. These documents automatically identified may not have been verified by the study sponsor.