Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001234101p
Ethics application status
Submitted, not yet approved
Date submitted
2/08/2019
Date registered
6/09/2019
Date last updated
6/09/2019
Date data sharing statement initially provided
6/09/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Use of rotational thromboelastometry (ROTEM) guided blood product utilisation in cirrhotic patients undergoing interventional procedures.
Scientific title
Use of ROTEM guided blood product utilisation in cirrhotic patients undergoing interventional procedures.
Secondary ID [1] 298873 0
Nil known
Universal Trial Number (UTN)
U1111-1237-7215
Trial acronym
PROTEM Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
chronic liver disease 313841 0
Condition category
Condition code
Oral and Gastrointestinal 312237 312237 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients randomized to the ROTEM arm will receive blood products guided by the ROTEM algorithm prior to their invasive procedure. 3.5ml of blood is to be collected into a citrate tube, which will be processed in the ROTEM analyzer on the same day of the procedure. Only one sample is required. Patients will then receive blood products as per the ROTEM algorithm.

As per the ROTEM algorithm patients will receive FFP, cryoprecipitate, platelets or no blood products based on the ROTEM EXTEM Clotting Time (CT), EXTEM (i.e. assessment of clot formation, fibrin polymerisation and fibrinolysis via the extrinsic pathway) amplitude at 10 minutes (A10) and FIBTEM (i.e. qualitative assessment of fibrinogen status) A10. The blood products given in the ROTEM arms will be compared to those used in the standard of care arm at each of the participating sites.

The interventions and patient care will be performed by the usual clinical teams, with aspects of the study (ROTEM measurement, blood product utilization supervised by the Principle Investigator at each site)
Intervention code [1] 315190 0
Other interventions
Comparator / control treatment
Standard of Care (SOC) arm
This will be the existing practice on the day associated with each hospital team and individual interventional radiologists, and local protocols if available. SOC at each site will be recorded for each patient. It is accepted that the standard practice may vary across different institutions and radiologists, reflecting the lack of current evidence based guidelines. The study is not designed to enforce a standard of care but rather to reflect real world current practice
Control group
Active

Outcomes
Primary outcome [1] 320941 0
Number of patients in each group requiring blood products.

3.5ml of blood is to be collected into a citrate tube, which will be processed in the ROTEM analyzer on the same day of the procedure. Only one sample is required. Patients will then receive blood products as per the ROTEM algorithm.

Patients in each arm who received blood products (e.g red cells, FFP, platelets, cryoprecipitate) will then be tallied.
Timepoint [1] 320941 0
On day of intervention
Secondary outcome [1] 373436 0
Number of units of red cells used.

3.5ml of blood is to be collected into a citrate tube, which will be processed in the ROTEM analyser on the same day of the procedure. Only one sample is required. Patients will then receive red cells as per the ROTEM algorithm.
Timepoint [1] 373436 0
On day of intervention
Secondary outcome [2] 373437 0
Cost of blood products in each arm of trial.

Costs will be assessed in Australian dollars (AUD) using local hospital costings.
Timepoint [2] 373437 0
On day of intervention
Secondary outcome [3] 373438 0
Total number of procedure-related bleeding events in each group.

Procedure-related bleeding events will be assessed by review of electronic and paper medical records, in addition to a patient follow up phone call at 30-days post procedure
Timepoint [3] 373438 0
On day of intervention
Secondary outcome [4] 373439 0
Serious adverse events including transfusion related adverse events.

Serious adverse events (SAEs) will be assessed by review of electronic and paper medical records, in addition to a patient follow up phone call at 30-days post procedure.

SAEs include:
- Procedure related bleeding or complications requiring readmission within 30 days or transfusion.
- Fluid overload
- Transfusion transmitted bacterial infection
- Acute and delayed haemolytic transfusion reactions
- Anaphylaxis
- Transfusion-related acute lung injury (TRALI)
Transfusion related adverse events will be assessed prospectively by clinical research team.
Timepoint [4] 373439 0
On day of intervention and the day after the intervention.
Secondary outcome [5] 373440 0
Rate of unnecessary blood product usage in standard of care arm (based on ROTEM profile).

An assessment will be made, using the ROTEM based algorithm, as to whether the blood product usage in the standard of care arm was necessary. i.e. -fell outside indications of ROTEM-guided blood product usage. The unnecessary usage will be described as both a count (number) and % of all blood products used in the standard of care arm.
Timepoint [5] 373440 0
On day of intervention
Secondary outcome [6] 374410 0
Number of units of fresh frozen plasma (FFP) used.

3.5ml of blood is to be collected into a citrate tube, which will be processed in the ROTEM analyzer on the same day of the procedure. Only one sample is required. Patients will then receive FFP as per the ROTEM algorithm.
Timepoint [6] 374410 0
On day of intervention
Secondary outcome [7] 374411 0
Number of units of platelets used.

3.5ml of blood is to be collected into a citrate tube, which will be processed in the ROTEM analyzer on the same day of the procedure. Only one sample is required. Patients will then receive platelets as per the ROTEM algorithm.
Timepoint [7] 374411 0
On the day of intervention.
Secondary outcome [8] 374412 0
Number of units of cryoprecipitate used.

3.5ml of blood is to be collected into a citrate tube, which will be processed in the ROTEM analyzer on the same day of the procedure. Only one sample is required. Patients will then receive cryoprecipitate as per the ROTEM algorithm.
Timepoint [8] 374412 0
-

Eligibility
Key inclusion criteria
Aged greater than or equal to 18 years
Able to give informed consent
Patients with coagulopathy (INR greater than or equal to 1.8 OR Platelet count less than or equal to 50,000) who require procedures with moderate to high risk of bleeding
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Known overt encephalopathy or cognitive impairment from other aetiologies
Non-English speakers

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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be randomized 1:1 to ROTEM guided or standard of care arms, via a call to the FMC randomization centre upon patient consent.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Patient anonymity will be maintained throughout this study, and patient name or any other identifying information will not be collected. De-identified patient data will instead be labelled with a unique study number. De-identified data will be entered into an Excel spreadsheet for analysis and reporting onto a password protected computer. Data will then be entered, collated and analysed using a Statistic Package for Social Sciences (SPSS).

The sample size has been calculated on the basis of the prior study by De Pietri et al (2016) that identified an 85% reduction in patients receiving blood products using a similar functional clotting assay named Thromboelastography (TEG). We have conservatively assumed a 50% reduction in patients receiving bloods products together with the following assumptions; 5% alpha error and 20% beta error. This provides a minimum recruitment target of 16 patients (8 per group). Standard statistical analyses, in consultation with our statistical investigator, Professor Richard Woodman, to compare differences between the ROTEM and SOC groups for the primary and secondary endpoints will be used. Differences for endpoints between groups will be assessed using Mann-Whitney’s U test which will be applied to compare nonparametric variables and chi-square test will be performed for categorical parameters. A two-tailed t test will be used for normally distributed data.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2019
Actual
Date of last participant enrolment
Anticipated
5/10/2020
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
16
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,WA
Recruitment hospital [1] 14384 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [2] 14385 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 14386 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [4] 14387 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 27393 0
5042 - Bedford Park
Recruitment postcode(s) [2] 27394 0
5000 - Adelaide
Recruitment postcode(s) [3] 27395 0
5112 - Elizabeth Vale
Recruitment postcode(s) [4] 27396 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 303418 0
Hospital
Name [1] 303418 0
Flinders Medical Centre
Country [1] 303418 0
Australia
Primary sponsor type
Hospital
Name
Flinders Medical Centre
Address
Flinders Drive
Bedford Park
SA 5042
Country
Australia
Secondary sponsor category [1] 303467 0
None
Name [1] 303467 0
Address [1] 303467 0
Country [1] 303467 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 303948 0
Southern Adelaide Clinical Human Research Ethics Committee (SAC HREC)
Ethics committee address [1] 303948 0
Flinders Medical Centre
Flinders Dr, Bedford Park SA 5042
Ethics committee country [1] 303948 0
Australia
Date submitted for ethics approval [1] 303948 0
22/07/2019
Approval date [1] 303948 0
Ethics approval number [1] 303948 0

Summary
Brief summary
Routine coagulation studies, such as INR and platelet count, do not accurately reflect the risk of bleeding in chronic liver disease (CLD) patients due to the complex changes in the coagulation system that occurs in CLD. Subsequently, the use of blood products in this setting is resource intensive and not evidence based. It is suggested that rotational thromboelastometry (ROTEM), can predict the risk of thrombosis and bleeding in CLD. The aim of this proposal is to study the effects of a ROTEM-guided blood product protocol in patients with CLD undergoing interventional procedures associated with a moderate to high risk of bleeding. Patients randomized to the ROTEM arm will receive blood products guided by the ROTEM algorithm, developed for the trial, prior to their invasive procedure. Blood products used will be compared to those used in the standard of care arm at each of the participating sites. It is anticipated that the study will show a significant reduction in blood product usage associated with the ROTEM arm. It is hoped that findings from this study will help establish improved evidence based guidelines for patients with CLD undergoing invasive procedures.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 95346 0
A/Prof Alan Wigg
Address 95346 0
Flinders Medical Centre
Flinders Dr, Bedford Park SA 5042
Country 95346 0
Australia
Phone 95346 0
+61 08 8204 5511
Fax 95346 0
Email 95346 0
[email protected]
Contact person for public queries
Name 95347 0
Dr Yasmina Tashkent
Address 95347 0
Flinders Medical Centre
Flinders Dr, Bedford Park SA 5042
Country 95347 0
Australia
Phone 95347 0
+61 08 8204 5511
Fax 95347 0
Email 95347 0
[email protected]
Contact person for scientific queries
Name 95348 0
Dr Yasmina Tashkent
Address 95348 0
Flinders Medical Centre
Flinders Dr, Bedford Park SA 5042
Country 95348 0
Australia
Phone 95348 0
+61 08 8204 5511
Fax 95348 0
Email 95348 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
3711Study protocol    378072-(Uploaded-02-08-2019-10-17-54)-Study-related document.docx
3712Informed consent form    378072-(Uploaded-02-08-2019-10-18-14)-Study-related document.docx



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.