Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619000386134
Ethics application status
Approved
Date submitted
14/02/2019
Date registered
12/03/2019
Date last updated
12/03/2019
Date data sharing statement initially provided
12/03/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
A search of novel biomarkers in detecting early allograft dysfunction afterliving donor liver transplantation
Scientific title
A lipidomics study in the early detection of early allograft dysfunction after living donor liver transplantation
Secondary ID [1] 297412 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
cirrhosis
 311577 0
end stage liver disease 311578 0
living donor liver transplantation 311579 0
early allograft dysfunction 311580 0
Condition category
Condition code
Oral and Gastrointestinal 310364 310364 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
We plan to enroll 120 living liver donors and 120 corresponding recipients over a 3-year period (roughly 40 pairs per year). Demographic data including age, gender, blood type, serum bilirubin, albumin, prothrombin levels, international normalized ratio (INR), serum alanine aminotransferase (ALT) activity, serum aspartate amniotransferase (AST) activity, serum gamma-glutamyltransferase (GGT) activity, platelet count, cholesterol profile and Model for End-Stage Liver Disease (MELD) score will be collected.

Sample collection
Blood and urine samples will be collected from the donors pre-operatively and from recipients at 6 different time points as follows: (T1) before induction of general anesthesia as baseline, (T2) 20 minutes after the start of anhepatic phase, (T3) 2 hours post reperfusion, (T4) day 1 post-operatively (T5) day 3 post-operatively, and (T6) day 7 post-operatively. Bile samples will be extracted from donors and recipients from their gallbladders after being removed by the surgeons. Recipients’ remnant liver tissues will also be extracted before livers are to be sent to pathology laboratory. Hemodynamic data will also be collected at these time points. The blood will be centrifuged immediately at 1,000 g, 4 °C, for 10 minutes to obtain plasma. Samples were stored at -80 °C until batch analysis. The routine biochemical data will be measured by the clinical laboratory within the hospital.
Intervention code [1] 313660 0
Early Detection / Screening
Comparator / control treatment
All recipients will be followed up postoperatively and divided into Early allograft dysfunction group (EAD) or non-EAD group according to their biochemical data on postoperative day 7.
EAD group is the comparator group.
Control group
Active

Outcomes
Primary outcome [1] 319091 0
On day 7 postoperatively, recipients will be assessed for the status of EAD or nonEAD using clinical parameters such as AST or ALT >2000; INR>1.6; bilirubin >10 via linkage to medical records
Timepoint [1] 319091 0
On postoperative day 7, EAD status will be assessed
Primary outcome [2] 319322 0
Metabolomic studies using NMR and LC-MS will be performed in search of new biomarkers differentiating EAD group from non-EAD group
Timepoint [2] 319322 0
Blood and urine samples collected from T1-T6 (T1: preoperatively; T2: 20 minutes after recipient hepatectomy; T3: 2 hours after reperfusion; T4: day 1 postoperatively;T5: day 3 postoperatively; T6: day 7 postoperatively) will be examined to search for novel biomarkers that distinguish EAD from non-EAD groups.
Secondary outcome [1] 366961 0
in hospital mortality
Timepoint [1] 366961 0
Medical records will be reviewed on whether or when the recipients are discharged uneventfully; in hospital mortality is documented on medical records and will be recorded in our study.

Eligibility
Key inclusion criteria
We plan to consecutively enroll recipients of living donor liver transplantation over a 3 year period
Minimum age
20 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria included a concurrent
septic or shocked status, an anticipated pulmonary hypertension with a preoperative pulmonary wedge pressure greater than 35 mmHg or refusal to provide informed consent.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Convenience sample
Timing
Prospective
Statistical methods / analysis
The study will be conducted over a 3 year period.
The continuous variables data were presented as the mean  standard deviation (SD), and
the independent sample t-test and the Mann-Whitney U test were used for the comparison of the EAD and non-EAD groups. The categorical data were presented as frequencies and compared using the chi-square test or the Fisher’s exact test. To identify an independent predictor of postoperative early allograft dysfunction, linear logistic regression analysis was performed. A receiver operator characteristic curve (ROC) was constructed, and the area under the ROC was used to measure the predictive accuracy and to compare between both groups. A p-value < 0.001 was considered to be statistically significant. All analyses were performed in R 3.3.2 and SAS 9.4 (SAS Institute, Cary, NC,
USA).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
16/10/2018
Date of last participant enrolment
Anticipated
9/10/2021
Actual
Date of last data collection
Anticipated
16/10/2021
Actual
Sample size
Target
120
Accrual to date
16
Final
Recruitment outside Australia
Country [1] 21281 0
Taiwan, Province Of China
State/province [1] 21281 0
ROC

Funding & Sponsors
Funding source category [1] 301980 0
Hospital
Name [1] 301980 0
Chang Gung Memorial Hospital
Country [1] 301980 0
Taiwan, Province Of China
Primary sponsor type
Hospital
Name
Chang Gung Memorial Hospital
Address
No. 5 Fuxing Street, Chang Gung Memorial Hospital
333, Taoyuan, Taiwan
Country
Taiwan, Province Of China
Secondary sponsor category [1] 301755 0
None
Name [1] 301755 0
Address [1] 301755 0
Country [1] 301755 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302659 0
Chang Gung Memorial Hospital IRB
Ethics committee address [1] 302659 0
No. 5 Fuxing Street, Chang Gung Memorial Hospital
333, Taoyuan, Taiwan
Ethics committee country [1] 302659 0
Taiwan, Province Of China
Date submitted for ethics approval [1] 302659 0
27/06/2018
Approval date [1] 302659 0
17/07/2018
Ethics approval number [1] 302659 0
201800847A3

Summary
Brief summary
Liver transplantation has become the ultimate treatment for patients with end-stage liver disease. EAD has a strong effect on graft failure and recipient mortality. In the study, we will examine the metabolomic differences between EAD and non-EAD patients among recipients of different etiologies. While EAD is defined as deterioration in the coagulation profiles and liver functions compared to non-EAD recipients on postoperative day 7, we expect to find earlier changes in the distribution of metabolites in EAD patients. A lipidomic study of their corresponding donors will also be conducted. Further in-depth metabolomic studies may reveal disturbances in the distribution of amino acid and lipids, providing potential biomarkers for the early detection of EAD.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 90966 0
Dr Hsin-I Tsai
Address 90966 0
No.5 Fuxing Street, Chang Gung Memorial Hospital
333, Taoyuan, Taiwan
Country 90966 0
Taiwan, Province Of China
Phone 90966 0
+886975366364
Fax 90966 0
Email 90966 0
tsaic@hotmail.com
Contact person for public queries
Name 90967 0
Dr Hsin-I Tsai
Address 90967 0
No.5 Fuxing Street, Chang Gung Memorial Hospital
333, Taoyuan, Taiwan
Country 90967 0
Taiwan, Province Of China
Phone 90967 0
+886975366364
Fax 90967 0
Email 90967 0
tsaic@hotmail.com
Contact person for scientific queries
Name 90968 0
Dr Hsin-I Tsai
Address 90968 0
No.5 Fuxing Street, Chang Gung Memorial Hospital
333, Taoyuan, Taiwan
Country 90968 0
Taiwan, Province Of China
Phone 90968 0
+886975366364
Fax 90968 0
Email 90968 0
tsaic@hotmail.com

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?

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
EmbaseA panel of biomarkers in the prediction for early allograft dysfunction and mortality after living donor liver transplantation.2021
N.B. These documents automatically identified may not have been verified by the study sponsor.