Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000457640
Ethics application status
Approved
Date submitted
22/07/2022
Date registered
3/05/2023
Date last updated
19/11/2023
Date data sharing statement initially provided
3/05/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
HUMPTY DUMPTY Feasibility Trial: Treatment options for management of bleeding during elective paediatric craniosynostosis surgery
Scientific title
HUMPTY DUMPTY feasibility trial: Physician versus viscoelastic assay-guided transfusion strategy for massive haemorrhage in elective cranial vault surgery
Secondary ID [1] 307419 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Massive blood transfusion in paediatric craniosynostosis surgery 326759 0
Condition category
Condition code
Anaesthesiology 323988 323988 0 0
Anaesthetics
Surgery 325643 325643 0 0
Other surgery
Neurological 325644 325644 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Non-red blood cell products will be transfused in line with protocol as displayed in ‘TEG6 guided massive transfusion strategy’. Should these results be unavailable despite a clinical need for blood volume replacement or haemodynamic instability, non-red cell products will be transfused at the anaesthetists’ discretion based on perceived haemostatic need and on recommendation of Queensland Children's Hospital Massive Transfusion Protocol.

As per standard institutional practice during craniosynostosis surgery bloods (including arterial blood gas, full blood count, Standard Coagulation profile) are performed on initiation of surgery, hourly, and cessation of surgery. Also it is performed if blood loss or clinician need requires and after non-red cell products have been administered. Typically surgery lasts for a duration of three hours, pending surgical difficulty or surgical complication. Each sampling represents a total volume of 2.1mls each time and sampling typically occurs 3-5 times preoperatively. The use of viscoelastic haemostatic assay via the TEG6s device (Haemonetics) will add an additional 1.3 mls each sample. Of which will be discussed as part of patient consent. This corresponds to the guidelines for the blood sampling in children for clinical research recommend a maximum of 3ml/kg over a 24-hour period or 10% of total blood volume over a period of 8 weeks.(1)

The protocol of non-red cell transfusion will be in line with our departmental Thromboelastography guideline, specifically 'HUMPTY DUMPTY TEG6s guided massive transfusion strategy'. This has been adapted from recommendations from Haemonetics Thromboelastography guidelines.(2) Specifically providing recommendations based on the parameters of the viscoelastic assay to replace specific products. For example if evidence of fibrinogen, platelet, factor deficiency will be replaced with cryoprecipitate, pooled platelets and fresh frozen plasma. Volume of non-red cell product given will be based on recommendations from our departmental thromboelastography guideline.

We will have a dedicated anaesthetic research nurse whom will be performing preoperative consent, performing the appropriate blood sampling and data collection. She is trained in quality assured thromboelastography sampling. The results of the sampling will be displayed in real time via computer display, and if not within normal range the anaesthetic clinician will transfuse according to protocol. It will be research nurse role to ensure the results are displayed and that the clinician has access to a visual protocol to guide protocol replacement. The research nurse will not provide recommendations nor interpretation of results. She will record data in real time, as per ‘case report form’ regarding feasibility and timing, amount and type of products and fluids transfused. Our trial is a feasibility trial primarily observing recruitment, and adherence to the intervention protocol. It will record transfusion requirements and deviation, including reasons, from protocol. The intention being to determine suitability for multi-site national trial.

TEG guided massive transfusion strategy was a protocol devised departmentally as a guideline within the Anaesthetic department of the Queensland Children’s Hospital. It utilises normal ranges given by Haemonetics responsible for the design of this specific viscoelastic haemostatic assay type.(3) Our protocol also utilises the Queensland Children’s Hospital Massive Transfusion Protocol. Currently we are looking to getting the current protocol approved through the QCH Blood Management Committee to be included in our hospital Massive transfusion protocol.(4)

The Haemonetics TEG6s Hemostasis Analyzer, will be utilised for the viscoelastic haemostatic assay.(3)

We have a pool of 5 anaesthetic specialists whom are responsible for performing the anaesthesia for craniosynostosis surgery.
The participants have previously undertaken and have received certification for analysis and interpretation of Haemonetics TEG6s Hemostasis Analyser via the web based Haemonetics TEG6s e-learning modules. This will be repeated prior to the co-design phase. The specialists have also previously received departmental education regarding the departmental TEG guided massive transfusion strategy . As such will be familiar with it’s use. Participants will be involved in 3, 1 hour focus groups during the study. The first being prior to commencement of recruitment, halfway through the recruitment period and after completion of recruitment). Identifying and clarify any enablers and barriers to implementation. As part of this process we will utilise a ‘Theoretical Framework of Acceptability Tool’ (5) and ‘Feasibility of Intervention Measure Tool’.(6)
During the codesign process, participants will be given the protocol and asked to provide feedback and suggestions with implementation.

(1)Royal College of Paediatrics and Child Health. Evidence statement. Major trauma and the use of tranexamic acid in children. November 2012.
(2)Haemonetics TEG6 e-learning: tegtraining.haemonetics.com
(3) Haemonetics TEG 6s Hemostasis Analyzer: https://teg.haemonetics.com
(4) Children’s Health Queensland Hospital and Health Service. Blood and Blood Products: Massive Haemorrhage Protocol (MHP) version 3.0
(5) Sekohn et. Al. ‘Acceptability of healthcare interventions: an overview of reviews and development of a theoretical framework”. BMC Health Services Research (2017) 17:88
(6) Weiner BJ, Lewis CC, Stanick C, et al. “Psychometric assessment of three newly developed implementation outcome measures”. Implementation Sci (2017) 12:108
Intervention code [1] 323856 0
Treatment: Other
Comparator / control treatment
Non-red blood cell products will be transfused as per anaesthetist discretion on perceived haemostatic requirement and surgical blood loss, assisted by available results from standard coagulation tests (APTT, PT, fibrinogen). Should these results be unavailable despite a clinical need for blood volume replacement, or haemodynamic instability, non-red blood products will be transfused based on perceived haemostatic need and on recommendations of Queensland Children’s Hospital Massive Transfusion protocol.

As per standard institutional practice during craniosynostosis surgery bloods (including arterial blood gas, full blood count, Standard Coagulation profile) are performed on initiation of surgery, hourly, and cessation of surgery. Also it is performed if blood loss or clinician need requires and after non-red cell products have been administered. Typically surgery lasts for a duration of three hours, pending surgical difficulty or surgical complication. Each sampling represents a total volume of 2.1mls each time and sampling typically occurs 3-5 times preoperatively. The use of viscoelastic haemostatic assay via the TEG6s device (Haemonetics) will add an additional 1.3 mls each sample. Of which will be discussed as part of patient consent. This corresponds to the guidelines for the blood sampling in children for clinical research recommend a maximum of 3ml/kg over a 24-hour period or 10% of total blood volume over a period of 8 weeks. (1)
Non-red cell products used will include cryoprecipitate, platelets and fresh frozen plasma
The comparator / control arm of the trial will be physician (anaesthetic driven) utilising standard coagulation tests as available to guide non-red blood cell products. Choice of type of product used will be up to anaesthetists discretion and perception of haemostatic need.
Our delegated research nurse, utilising our case report form will monitor adherence to and / or fidelity of treatment specifically non-red blood cell products given and indications for doing so.

1)Royal College of Paediatrics and Child Health. Evidence statement. Major trauma and the use of tranexamic acid in children. November 2012.
Control group
Active

Outcomes
Primary outcome [1] 332063 0
Primary Outcome 1
o Patient recruitment and adherence to interventional and control study protocol of 80%. As assessed by audit of study database.
Timepoint [1] 332063 0
Upon conclusion of study
Secondary outcome [1] 412043 0
`Any change in red blood cell transfusion volume as assessed by medical record review.
Timepoint [1] 412043 0
Assessed from the time of commencing surgery to 24 hours post-completion of surgery.
Secondary outcome [2] 412171 0

Significant adverse events requiring treatment defined as the following (assessed by study specific log / data collection form undertaken by specific research assistant perioperatively and by review of medical record review 1 month, 3 month and 12 months post-surgery)
Cardiac arrest
Mortality
Or any life-threatening medical event or reaction which the clinician believes may be study related.
Hypotension - Unanticipated drop in expected baseline mean arterial pressure by 20%.
Bradycardia of <60/min
Transfusion reaction or Thrombotic Events
Timepoint [2] 412171 0
Monitored continuously during the surgical procedure by anaesthetist and research assistant and assessed by review of medical record review 1 month, 3 month and 12 months post-surgery
Secondary outcome [3] 417710 0
o Anaesthetist protocol acceptability and feasibility outlined by a ‘Theoretical Framework Acceptability Tool’1 (a questionnaire modified from the referenced article) and ‘Acceptability of Intervention Measure, Intervention Appropriateness Measure, Feasibility of Intervention Measure Tool’2 (a questionnaire modified from the referenced article, utilising a 5-point Likert scale). These will be written questionnaires, with information collated upon completion.
1. Sekohn et. Al. ‘Acceptability of healthcare interventions: an overview of reviews and development of a theoretical framework”. BMC Health Services Research (2017) 17:88
2. Weiner BJ, Lewis CC, Stanick C, et al. “Psychometric assessment of three newly developed implementation outcome measures”. Implementation Sci (2017) 12:108
Timepoint [3] 417710 0
These will be conducted prior to initiation, after 6 months following initiation and upon completion of study (18 months following initiation)

Eligibility
Key inclusion criteria
Elective total cranial vault and / or bifrontal orbital advancement surgery for craniosynostosis with anticipated massive blood loss (> 40mls/kg)
Minimum age
No limit
Maximum age
3 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Congenital or acquired bleeding disorder (known or suspected); Perioperative anti-platelet and / or anticoagulant use
Previous cranial vault surgery
Refusal for consent
Intercurrent illness rendering surgery or anaesthesia unsafe

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)
Central randomisation via computer will be used to achieve allocation concealment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be allocated to a treatment arm using a computer-based randomisation schedule and an allocation of 1:1 per treatment arm.
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
The proposed study is a feasibility pilot study and will inform statistical power calculations for any future larger studies. The sample size for the pilot study will be a convenience sample over a 12-18 month period and is anticipated to be 20 patients (10 per arm) based on audit of previous case numbers in our facility.

Descriptive statistics will be used to report on the baseline characteristics of the total study cohort and each treatment group. As this is a pilot trial, formal statistical comparisons will not be undertaken. All outcomes will be presented as estimate along with 95% confidence interval; feasibility outcomes will be presented only for the total cohort, while safety and efficacy outcomes will be presented for the total cohort, as well as per treatment group. Analyses will be undertaken using intention-to-treat, however the number and type of protocol deviations will be reported to assist in feasibility assessment.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
22/11/2023
Actual
Date of last participant enrolment
Anticipated
20/11/2024
Actual
Date of last data collection
Anticipated
12/08/2025
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 22854 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 38156 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 311695 0
Other Collaborative groups
Name [1] 311695 0
SPANZA (Society of Paediatric Anaesthetists of New Zealand and Australia)
Country [1] 311695 0
Australia
Funding source category [2] 315255 0
Other Collaborative groups
Name [2] 315255 0
Australian and New Zealand College of Anaesthetists (ANZCA)
Country [2] 315255 0
Australia
Primary sponsor type
Hospital
Name
Queensland Children's Hospital
Address
501 Stanley Street, South Brisbane, QLD, 4511
Country
Australia
Secondary sponsor category [1] 313366 0
None
Name [1] 313366 0
Address [1] 313366 0
Country [1] 313366 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311148 0
Queensland Children's Hospital Human Research and Ethics Committee
Ethics committee address [1] 311148 0
Ethics committee country [1] 311148 0
Australia
Date submitted for ethics approval [1] 311148 0
16/05/2022
Approval date [1] 311148 0
19/05/2022
Ethics approval number [1] 311148 0
HREC/22/QCHQ/69056

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

Contacts
Principal investigator
Name 120110 0
Dr Stuart Blain
Address 120110 0
Queensland Children's Hospital
501 Stanley Street, South Brisbane, 4101, QLD
Country 120110 0
Australia
Phone 120110 0
+61 400080384
Fax 120110 0
Email 120110 0
[email protected]
Contact person for public queries
Name 120111 0
Stuart Blain
Address 120111 0
Queensland Children's Hospital
501 Stanley Street, South Brisbane, 4101 QLD
Country 120111 0
Australia
Phone 120111 0
+61 400080384
Fax 120111 0
Email 120111 0
[email protected]
Contact person for scientific queries
Name 120112 0
Shannon Morrison
Address 120112 0
Queensland Children's Hospital
501 Stanley Street, South Brisbane, 4101, QLD
Country 120112 0
Australia
Phone 120112 0
+61 423526705
Fax 120112 0
Email 120112 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual participant data of published results only
When will data be available (start and end dates)?
3 months following publication and ending 5 years following main results publication
Available to whom?
De-identified data on a case-by-case basis at the discretion of Principle Investigator Dr Stuart Blain and Primary Sponsor of researchers with a sound proposal
Available for what types of analyses?
De-identified data on a case-by-case basis at the discretion of Principle Investigator Dr Stuart Blain and Primary Sponsor of researchers with a sound proposal
How or where can data be obtained?
Access subject to approval by Principal Investigator Dr Stuart Blain [email protected]


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.