Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000499583
Ethics application status
Approved
Date submitted
20/03/2024
Date registered
23/04/2024
Date last updated
23/04/2024
Date data sharing statement initially provided
23/04/2024
Date results provided
23/04/2024
Type of registration
Retrospectively registered

Titles & IDs
Public title
Massive transfusion in adult patients undergoing liver transplantation
Scientific title
Ultra-massive transfusion in adult patients during liver transplantation: a retrospective single centre observational study
Secondary ID [1] 311456 0
None
Universal Trial Number (UTN)
U1111-1303-6538
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Liver transplantation 332754 0
Outcome after ultra-massive blood transfusion 332755 0
Condition category
Condition code
Surgery 329476 329476 0 0
Surgical techniques
Anaesthesiology 329746 329746 0 0
Anaesthetics
Oral and Gastrointestinal 330088 330088 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This study will use patient data from a single-centre to investigate the association of ultra-massive transfusion and in-hospital complications in adult patients undergoing liver transplantation from 1 January 2019 to 1 January 2023.

Ultra-Massive Transfusion is a relatively new term that has generally been accepted to describe the transfusion of >20 units of packed red blood cells (RBC) in 24 hours.

Using routinely collected in-hospital data from the patients electronic medical records, this study will identify the proportion of adult patients who undergo liver transplantation who receive an ultra-massive transfusion. Ultra-massive fluid transfusion will defined a priori as a total transfusion > 20 liters of crystalloids, colloids, blood, and coagulation factors adminsitered intraoperatively and within 24-hours post surgery.

Pre-operative risk factors for necessitating ultra-massive transfusion will be investigated. Secondary aims will investigate the relationship between the amount of pack red blood cells transfused and postoperative complications until hospital discharge. Mortality will be collected until 3 years post transplant. Finally, we will evaluate the effects of the co-transfused fresh frozen plasma to packed red blood cells ratio on postoperative complications. and mortality up until 3 years post-transplant.
Intervention code [1] 328086 0
Not applicable
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 337537 0
The proportion of adult patients who receive an ultra massive transfusion during liver transplantation
Timepoint [1] 337537 0
Intraoperatively and during the first 24 hours postoperatively
Secondary outcome [1] 432251 0
To investigated the relationship between the amount of pack RBC transfused during liver transplantation and postoperative complications. Complications will be assessed and graded by the Clavier Dindo Classification system. Complications will include bleeding requiring blood and blood products, bile leak, hepatic artery or vein thrombosis, liver abscess, return to theatre for bleeding, infection, primary graft non-function, or re-transplantation or readmission within 30 days post transplant.
Timepoint [1] 432251 0
Complications will be assessed postoperatively until 30 days post hospital discharge.
Secondary outcome [2] 432252 0
To evaluated the association of coagulation therapy administered and the number of red blood units transfused intraoperatively until hospital discharge.
Timepoint [2] 432252 0
Intraoperatively until 24-hours post surgery.
Secondary outcome [3] 432253 0
Length of hospital stay
Timepoint [3] 432253 0
From time of admission to time of hospital discharge (or death, if patient dies as an inpatient)
Secondary outcome [4] 434338 0
To investigated the relationship between the amount of pack RBC transfused during liver transplantation and mortality.
Timepoint [4] 434338 0
Mortality will be measured at one, two, and three years post transplant.

Eligibility
Key inclusion criteria
Inclusion Criteria:
1. Adult patient
2. Undergoing liver transplantation surgery
3. Patient receives ultra-massive transfusion
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Paediatric patients

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Retrospective
Statistical methods / analysis
Based on a preliminary search, we expect the total sample size for the project to be between 100-200 patients.

This sample size is sufficient to meet the research aims and answer the research questions because it provides accurate data that facilitates understanding of the extent of association between ultra-massive transfusion and post-operative outcomes in adult patients undergoing liver transplantation surgery.

The statistical analysis plan has been designed with a biostatistician.

All statistical analysis will be performed with R 4.3.2( R: A language and environment for statistical computing, R core Team (2023), Vienna, Austria). Continuous variables will be evaluated for normality assumption using Shapiro’s test and visual check of Q-Q plots. Data will be presented with mean ± standard deviation(SD), median (1st to 3rd quartiles) [Min:Max], or number of cases (percentile) for the descriptive statistics, and any estimated values will be described with 95% confidence intervals (CI).

Statistical results will be presented with P values and corresponding effect sizes. A 2-sided P value below 0.05 will be considered statistical significance based on the null hypothesis significance testing, and the number of effects will be evaluated with the estimated effect sizes.

For the primary objective, we will explore meaningful categorization criteria for the number of units of intraoperative pack RBC transfused. Several data points of the amount of pack RBC transfusion will be evaluated: arithmetic mean, non-parametric statistics (median, quantiles), best-coordinated point by Receiver-Operator Curve (ROC) analysis, and Youden index, cut points from a decision tree model.

The response variables will be categorized as worst complication grade (no complication to Clavien Dindo grade IIIa vs. Clavien Dindo grade IIIb or higher) and number of complications (no complications to two complications vs. three or more complications). In the context of data balance between categorized groups and unadjusted comparative results, we will formulatesubgroups according to the amount of pack RBC transfusion: less than ten units, 10 to 14 units, and 15 or more units.

The effect of pack RBC transfusion subgroups and administered blood volume during surgery will be adjusted with the following variables: age, body mass index, MELD score, preoperative prothrombin time, preoperative albumin, preoperative platelet, preoperative haemoglobin, preoperative fibrinogen, use of veno-veno bypass, surgery duration, intraoperative noradrenaline (highest dose), baseline pO2, HCO3-, calcium, lactate and d-dimer.

The Bayesian approach will be applied to the logistic or linear regression modeling to estimate the adjusted coefficient of subgroups.

The Markov Chain Monte Carlo (MCMC) estimation process will be conducted. Fitted models will be evaluated with appropriate MCMC diagnostic plots, including posterior distribution density and trace plots. Predicted values from the fitted model will be assessed with a posterior predict checks plot.

Residuals will be evaluated with a visual check of residual plot and residual distribution. Auto-correlation will be diagnosed using visualization of auto-correlation of MCMC samples. The R ^ and effective sample size (ESS) will also be evaluated for MCMC diagnostics. ESS, bulk ESS, and tail ESS will be evaluated with a visual check of ESS bar graphs for each parameter.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
26/03/2024
Date of last participant enrolment
Anticipated
Actual
17/04/2024
Date of last data collection
Anticipated
Actual
19/04/2024
Sample size
Target
105
Accrual to date
Final
95
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 26221 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 42189 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 315735 0
Hospital
Name [1] 315735 0
Austin Health - Department of Anaesthesia
Country [1] 315735 0
Australia
Primary sponsor type
Hospital
Name
Austin Health - Department of Anaesthesia
Address
Country
Australia
Secondary sponsor category [1] 317849 0
None
Name [1] 317849 0
Address [1] 317849 0
Country [1] 317849 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314600 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 314600 0
Ethics committee country [1] 314600 0
Australia
Date submitted for ethics approval [1] 314600 0
09/03/2024
Approval date [1] 314600 0
25/03/2024
Ethics approval number [1] 314600 0
HREC/105884/Austin-2024

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

Contacts
Principal investigator
Name 132138 0
Prof Laurence Weinberg
Address 132138 0
Department of Anaesthesia, 145 Studley Road, Austin Health, Heidelberg VIC 3084
Country 132138 0
Australia
Phone 132138 0
+61 3 9496 3800
Fax 132138 0
Email 132138 0
[email protected]
Contact person for public queries
Name 132139 0
Prof Laurence Weinberg
Address 132139 0
Department of Anaesthesia, 145 Studley Road, Austin Health, Heidelberg VIC 3084
Country 132139 0
Australia
Phone 132139 0
+61 3 9496 3800
Fax 132139 0
Email 132139 0
[email protected]
Contact person for scientific queries
Name 132140 0
Prof Laurence Weinberg
Address 132140 0
Department of Anaesthesia, 145 Studley Road, Austin Health, Heidelberg VIC 3084
Country 132140 0
Australia
Phone 132140 0
+61 3 9496 3800
Fax 132140 0
Email 132140 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
Participant confidentiality will be maintained by only reporting aggregate results.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
21905Ethical approval  [email protected] 387270-(Uploaded-01-04-2024-19-09-20)-Study-related document.pdf
21906Statistical analysis plan  [email protected]



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.