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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12626001300369
Ethics application status
Help: Ethics application status
Approved
Date submitted
Help: Date submitted
16/10/2026
Date registered
Help: Date registered
28/10/2026
Date last updated
Help: Date last updated
28/10/2026
Date data sharing statement initially provided
Help: Data sharing statement date
28/10/2026
Type of registration
Help: Type of registration
Retrospectively registered

Titles & IDs
Public title
Efficacy and safety of prehospital fibrinogen early in severe trauma study: A feasibility and two arm phase II study (PRE-FEISTY II)(Stage 2).
Scientific title
Efficacy and safety of prehospital fibrinogen early in severe trauma study: A feasibility and two arm phase II study (PRE-FEISTY II)(Stage 2).
Additional trial identifiers [1] 310129 0
None
Universal Trial Number (UTN)
Trial acronym
PRE-FEISTY II (stage 2)
Related trial records
This is part of an adaptive trial, the first arm of which is stage 1 (ACTRN12623000812695). This part (stage 2) follows on from stage 1, adding in randomisation to one of two arms. In data analysis the two trials will be treated as a functional unit, with the intervention arm consisting of 53 patients, and the control arm consisting of 30 patients).

Health condition
Health condition(s) studied:
Acute traumatic haemorrhage 330697 0
Condition category
Condition code
Blood 327527 327527 0 0
Clotting disorders
Emergency medicine 327528 327528 0 0
Other emergency care
Injuries and Accidents 327529 327529 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
Intravenous or intraosseous adminstration of three vials (approximately 3g) of fibrinogen concentrate (RiaStap®) following the conclusion of initial resuscitation and stabilisation, anticipated to be in the timeframe of 15-60 minutes following the arrival of a prehospital medical team.
The intervention will be delivered once.
Adherence to the intervention will be monitored by regular ongoing audit of all patients treated by our service who receive prehospital blood transfusion. This audit is already embedded in our routine clinical governance procedures.
Intervention code [1] 326532 0
Treatment: Drugs
Description of the comparator or control
Stage two - control group will be standard care alone (i.e. they will receive the same treatment as the intervention group, but without the administration of fibrinogen concentrate. No placebo will be administered (i.e. this is an open-label trial).
Control group
Active

Outcomes
Primary outcome [1] 335386 0
Percentage of patients with a fibrinogen level >2.0 g/L assessed by laboratory testing following hospital arrival.
Timepoint [1] 335386 0
On first testing following arrival in hospital (anticipated within 30 minutes of hospital arrival).
Secondary outcome [1] 424253 0
In-hospital mortality (alive/dead). Assessed by review of the electronic medical record by a member of the research team.
Timepoint [1] 424253 0
24 hours following hospital arrival.
Secondary outcome [2] 424254 0
Length of stay in acute hospital in calendar days - assessed by review of the electronic medical record by a member of the research team.
Timepoint [2] 424254 0
At hospital discharge or death
Secondary outcome [3] 424255 0
Number of days of mechanical ventilation.
Timepoint [3] 424255 0
At hospital discharge or death. Assessed by review of the electronic medical record by a member of the research team.
Secondary outcome [4] 424256 0
Total number of blood products (packed cells, plasma, platelets and cryoprecipitate) administered. Assessed by review of the electronic medical record by a member of the research team.
Timepoint [4] 424256 0
24 hours from hospital arrival.
Secondary outcome [5] 424257 0
Requirement for a haemorrhage control procedure - either surgical operation or via interventional radiology. Assessed by review of the electronic medical record by a member of the research team.
Timepoint [5] 424257 0
Within 24 hours of hospital arrival.
Secondary outcome [6] 424258 0
Radiologically proven occurrence of venous thromboembolic disease (pulmonary embolism or deep vein thrombosis). Assessed by review of the electronic medical record by a member of the research team.
Timepoint [6] 424258 0
Within 28 days of hospital admission.

Eligibility
Key inclusion criteria
Adult patient (aged greater than or equal to 18 years)
Judged to have ongoing haemorrhage by the treating clinician.
Receiving prehospital blood transfusion.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Healthy volunteers
No
Key exclusion criteria
1. Injury judged incompatible with survival
2. Enrolment unable to occur within 6 hours of injury
3. Known pregnancy
4. Known genetic or drug induced coagulation disorder.
5. Known objection to blood products
6. Dedicated prior fibrinogen replacement
7. Participation in a competing 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)
Following identification of a potential participant, a member of the treating team will open a smartphone-based application, enter basic demographics, and check inclusion and exclusion criteria.
After determining eligibility, they will click the 'randomise' button on the application, and the treatment allocation will be displayed.
From this point forwards, the treating clinician will be aware of the allocated treatment - i.e. this is an open-label trial.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be performed using an on-line web-based computer-generated process (REDCap). Participants will be randomised to receive fibrinogen concentrate and standard care or standard care alone.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis
This should be read in conjunction with the registration for Stage 1 of this study (registration number ACTRN12623000812695.

Conventional phase II clinical trials use either a single- or multi-arm comparison scheme to examine the therapeutic effects of the experimental drug. Both single- and multi-arm evaluations have their own merits; for example, single-arm phase II trials are easy to conduct and often require a smaller sample size, while multi-arm trials are randomised and typically lead to a more objective comparison. To bridge the single- and double-arm schemes in one trial, a two-stage design has been selected, in which the first stage takes a single-arm comparison of fibrinogen concentrate with the base normal fibrinogen rate (standard major trauma treatment alone) and the second stage imposes a two-arm comparison by adding an active control arm. The design is calibrated using the detectable treatment difference to balance the trade-offs between futility termination, power, and sample size. The base normal fibrinogen rate (standard major trauma treatment alone) is assumed to be 33% (p_0 greater than or equal to 0.33) which is based on the expert opinion of study investigators. The desirable target rate is 58% (p_1 is greater than or equal to 0.58).

The design parameters required are the number of subjects in the experimental arm of the single arm stage (n_1), the number of subjects in each arm of the double-arm stage (n_2) and the minimum number of responses to achieve in the single-arm stage in order for the trial to proceed on to the next stage (r_1). Similar to sample size calculations in other study designs, calibration of these design parameters required the minimally required level for the response rate to be clinically meaningful (p_0), the desirable target rate (p_1), the type I error rate constraints for both stages (alpha_1,alpha_2) and the type II error rate constraints for both stages, (beta_1,beta_2)

These were specified as:
p_0=0.33,p_1=0.58,alpha_1=0.2,beta_1=0.1 (power=90%),a_2=0.1,beta_2=0.2 (power=80%)

The optimal set of (n_1,n_2,r_1) was chosen by minimising the average sample number (ASN), which is the average of the expected sample size under the null (ESS_0) and under the alternative (ESS_1) hypotheses, i.e., ASN=(ESS_0+ESS_1)/2, with
ESS_0=n_1 + 2n_2 P(x_1>r_1¦p_E=p_0 )
ESS_1=n_1 + 2n_2 P(x_1>r_1¦p_E=p_1 )

The computation of the expected sample sizes ESS_0 and ESS_1 was based on the probability of continuing to the second stage under the null and the alternative hypotheses, respectively. (When the null hypothesis is true, the trial would ideally be terminated early for sample size saving. On the other hand, when the alternative hypothesis is true, we would want the trial to continue on to the second stage.)

The reason for using ASN as the criterion is because it takes into account both the null and alternative scenarios.
The following numerical algorithm was used to optimise n_1,n_2,r_1:
Set n_1 from 10 to N, where N is the required sample size in each arm under a conventional two-arm scheme with equal randomisation and the type I and type II error rates of alpha_2 and beta_2.
Given n_1, find the value of r_1 such that the type I and type II error rates in Equations (1) and (2) are below alpha_1 and beta_1, respectively.

Set the critical value for the Z-test to be c=Z_a with a_2 given in Equation (3). Given n_1 and r_1, find the value of n_2 that satisfies the type II error rate constraint of beta_2 according to Equation (4).

Enumerate all possible values of (n_1, n_2, r_1) and choose the one that minimises the ASN.

Results of samples size calculations:
Number of participants required in stage one, n_1=23
Number of participants required in each arm of stage two, n_2=30
Total number of participants =83

Results:

Descriptive statistics will be used to report the results of the stage 1 (single-arm) element of this trial (discussed in separate registration ACTRN12623000812695).

Differences between groups in the second stage (which will incorporate results from stage 1 to increase power) will be determined using the Chi-squared test for categorical data, and either the student's t-test or the Mann-Whitney test depending on the normality of distribution.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
11/09/2024
Date of last participant enrolment
Anticipated
30/11/2026
Actual
Date of last data collection
Anticipated
30/12/2026
Actual
Sample size
Target
60
Accrual to date
57
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 25186 0
Gold Coast University Hospital - Southport
Recruitment hospital [2] 25187 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [3] 25188 0
Westmead Hospital - Westmead
Recruitment hospital [4] 25189 0
Liverpool Hospital - Liverpool
Recruitment hospital [5] 25190 0
St George Hospital - Kogarah
Recruitment hospital [6] 25191 0
John Hunter Hospital - New Lambton
Recruitment hospital [7] 25192 0
Lismore Base Hospital - Lismore
Recruitment hospital [8] 25193 0
Orange Health Service - Orange
Recruitment postcode(s) [1] 40856 0
4215 - Southport
Recruitment postcode(s) [2] 40857 0
2065 - St Leonards
Recruitment postcode(s) [3] 40858 0
2145 - Westmead
Recruitment postcode(s) [4] 40859 0
2170 - Liverpool
Recruitment postcode(s) [5] 40860 0
2217 - Kogarah
Recruitment postcode(s) [6] 40861 0
2305 - New Lambton
Recruitment postcode(s) [7] 40862 0
2480 - Lismore
Recruitment postcode(s) [8] 40863 0
2800 - Orange

Funding & Sponsors
Funding source category [1] 314290 0
Government body
Name [1] 314290 0
NSW Ambulance
Country [1] 314290 0
Australia
Primary sponsor type
Government body
Name
NSW Ambulance
Address
Locked Bag 105RozelleNSW2039
Country
Australia
Secondary sponsor category [1] 316240 0
None
Name [1] 316240 0
Address [1] 316240 0
Country [1] 316240 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313406 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 313406 0
Ethics committee country [1] 313406 0
Australia
Date submitted for ethics approval [1] 313406 0
09/09/2022
Approval date [1] 313406 0
29/11/2022
Ethics approval number [1] 313406 0
2022/ETH00820

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

Contacts
Principal investigator
Name 128042 0
Dr Ian Ferguson
Address 128042 0
Aeromedical Retrieval ServiceNSW Ambulance 33 Nancy Ellis Leebold DriveBankstown AerodromeNSW 2200
Country 128042 0
Australia
Phone 128042 0
+61 0403 859555
Fax 128042 0
Email 128042 0
[email protected]
Contact person for public queries
Name 128043 0
Ian Ferguson
Address 128043 0
Aeromedical Retrieval ServiceNSW Ambulance 33 Nancy Ellis Leebold DriveBankstown AerodromeNSW 2200
Country 128043 0
Australia
Phone 128043 0
+61 0403 859555
Fax 128043 0
Email 128043 0
[email protected]
Contact person for scientific queries
Name 128044 0
Ian Ferguson
Address 128044 0
Aeromedical Retrieval ServiceNSW Ambulance 33 Nancy Ellis Leebold DriveBankstown AerodromeNSW 2200
Country 128044 0
Australia
Phone 128044 0
+61 0403 859555
Fax 128044 0
Email 128044 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No
No IPD sharing reason/comment: This study is being conducted under a waiver of informed consent. Whilst consent for data use will be sought subsequent to enrolment, we are taking steps to minimise the risk of holding data in these circumstances.



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.