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Trial registered on ANZCTR


Registration number
ACTRN12615000446561
Ethics application status
Approved
Date submitted
26/03/2015
Date registered
8/05/2015
Date last updated
15/02/2019
Date data sharing statement initially provided
15/02/2019
Date results information initially provided
15/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Does metabolomic incompatibility between living liver donors and recipients predict early allograft dysfunction in liver transplantation?
Scientific title
In recipients of liver transplantation, does metabolomic incompatibility to donors lead to early allograft dysfunction?
Secondary ID [1] 285842 0
nil is known
Universal Trial Number (UTN)
U1111-1168-7315
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
liver transplantation 294576 0
Early allograft dysfunction 294577 0
Metabolomic incompatibilty between donors and recipients 294578 0
Condition category
Condition code
Metabolic and Endocrine 294880 294880 0 0
Other metabolic disorders
Surgery 294881 294881 0 0
Other surgery
Cancer 295167 295167 0 0
Liver

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Blood and urine samples will be collected peri-operatively. Samples of liver donors will be collected before and after general anesthesia is conducted in the operating room. Samples of the recipients will be collected at several time points: (T1) before induction as baseline, (T2) after induction during general anesthesia, (T3) before the end of anhepatic phase, (T4) 2 hours post reperfusion, (T5) day 1 post-operatively and (T6) day 5 post-operatively. Hemodynamic data will also be collected at these time points.

At day 7, liver transplant clinical outcomes will be assessed and classified as early allograft dysfunction (EAD) for grafts meeting one criterion or more (bilirubin greater than or equal to 10mg/dl, INR greater than or equal to 1.6, alanine (ALT) or aspartate (AST) amniotransferase greater than 2000IU/L within the first 7 days; as immediate graft function (IGF) for grafts with values below the cut-off points mentioned above; and as primary non function (PNF) for patients with irreversible graft dysfunction without detectable technical or immunological problems.

Intervention code [1] 291493 0
Not applicable
Comparator / control treatment
Healthy living liver donors are enrolled and their blood and urine samples are collected before and after general anesthesia is conducted.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 294641 0
Liver transplant clinical outcomes will be assessed and classified as early allograft dysfunction (EAD) for grafts meeting one criterion or more (bilirubin greater than or equal to 10mg/dl, INR greater than or equal to 1.6, alanine (ALT) or aspartate (AST) amniotransferase greater than 2000IU/L within the first 7 days; as immediate graft function (IGF) for grafts with values below the cut-off points mentioned above; and as primary non function (PNF) for patients with irreversible graft dysfunction without detectable technical or immunological problems.
Timepoint [1] 294641 0
At day 7 after liver transplantation is conducted
Secondary outcome [1] 313784 0
Metabolomic data of liver donors and recipients. The blood and urine samples will be analyzed using hydrogen-1 nuclear magnetic resonance (1H-NMR) and lipid chromatography-mass spectrometry (LC-MS).The laboratory analysis will be studied with the clinical outcomes of liver transplantation in elucidating the possible mechanisms during transplantation and the possible factors influencing the success of organ transplantation.
Timepoint [1] 313784 0
Blood and urine samples will be collected peri-operatively. Samples of donors will be collected before and after general anesthesia in the operating room. Samples of the recipients will be collected at several time points: (T1) before induction as baseline, (T2) after induction during general anesthesia, (T3) before the end of anhepatic phase, (T4) 2 hours post reperfusion, (T5) day 1 post-operatively and (T6) day 5 post-operatively. Metabolomic studies will be conducted from these blood and urine samples and their trends will be studied in relation to the primary outcome.

Eligibility
Key inclusion criteria
Inclusion criteria for donor:
1. No history of liver disease
2. No medical history of cancer in the last 10 years
3. No HBsAg, no hepatitis C virus or HIV antibodies

Inclusion criteria for recipient:
1. Patients with liver cirrhosis or hepatocellular carcinoma in need for liver transplantation

Minimum age
20 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria for donor:
1. Refusal to sign informed consent
2. Age <20 years old
Exclusion criterial for recipient:
1. Refusal to sign informed consent
2. Recent sepsis or shock status
3. History of hepatoencephalopathy
4. History of hepatorenal syndrome
5. Anticipated pulmonary hypertension with preoperative pulmonary wedge pressure >35mmHg

Study design
Purpose
Duration
Selection
Timing
Statistical methods / analysis
Metabolomic software, GeneSpring MS, Markerlyn XS & Metaboanalyst, will be used for multivariate data analysis and representation. For structural identification of target metabolite, standards will be operated under identical chromatographic conditions with that of the profiling experiment. MS and MS/MS analyses are performed in the same conditions.
The number of participants expected to enroll the study is calculated based on the number of liver transplantation conducted in our institution per year. In average, 2 liver transplantations are conducted per week, and we aim to enroll 120 living liver donors and 120 recipients.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 6774 0
Taiwan, Province Of China
State/province [1] 6774 0
Taiwan

Funding & Sponsors
Funding source category [1] 290989 0
Hospital
Name [1] 290989 0
Chang Gung Memorial Hospital
Address [1] 290989 0
No.5, Fusing St., Gueishan Township, Taoyuan County 333, Taiwan (R.O.C.)
Country [1] 290989 0
Taiwan, Province Of China
Primary sponsor type
Individual
Name
Dr. Huang-Ping Yu
Address
Chang Gung Memorial Hospital
No.5, Fusing St., Gueishan Township, Taoyuan County 333, Taiwan (R.O.C.)
Country
Taiwan, Province Of China
Secondary sponsor category [1] 289669 0
Individual
Name [1] 289669 0
Dr. Hsin-I Cynthia
Address [1] 289669 0
Chang Gung Memorial Hospital
No.5, Fusing St., Gueishan Township, Taoyuan County 333, Taiwan (R.O.C.)
Country [1] 289669 0
Taiwan, Province Of China

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292578 0
Chang Gung Memorial Hospital
Ethics committee address [1] 292578 0
No.5, Fusing St., Gueishan Township, Taoyuan County 333, Taiwan (R.O.C.)
Ethics committee country [1] 292578 0
Taiwan, Province Of China
Date submitted for ethics approval [1] 292578 0
Approval date [1] 292578 0
17/03/2015
Ethics approval number [1] 292578 0

Summary
Brief summary
The liver is an essential organ in human body because it possesses synthetic, metabolic, secretory and excretory functions. For patients with acute and chronic end-stage liver disease, liver transplantation has been established as a viable treatment, and its success partly depends on proper organ retrieval, adequate donor assessment and optimal peri-operative conditions. The aim of the study is to determine the association of metabolomic incompatibility between donor and recipient andto predict early allograft dysfunction in liver transplantation.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 381 381 0 0

Contacts
Principal investigator
Name 53514 0
Prof Huang-Ping Yu
Address 53514 0
Chang Gung Memorial Hospital
No.5, Fusing St., Gueishan Township, Taoyuan County 333, Taiwan (R.O.C.)
Country 53514 0
Taiwan, Province Of China
Phone 53514 0
+886-403-2324
Fax 53514 0
Email 53514 0
yuhp2001@cgmh.org.tw
Contact person for public queries
Name 53515 0
Dr Hsin-I Cynthia Tsai
Address 53515 0
Chang Gung Memorial Hospital
No.5, Fusing St., Gueishan Township, Taoyuan County 333, Taiwan (R.O.C.)
Country 53515 0
Taiwan, Province Of China
Phone 53515 0
+886-403-2324
Fax 53515 0
Email 53515 0
tsaic@hotmail.com
Contact person for scientific queries
Name 53516 0
Dr Hsin-I Cynthia
Address 53516 0
Chang Gung Memorial Hospital
No.5, Fusing St., Gueishan Township, Taoyuan County 333, Taiwan (R.O.C.)
Country 53516 0
Taiwan, Province Of China
Phone 53516 0
+886-403-2324
Fax 53516 0
Email 53516 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?
Study protocol
Statistical analysis plan
Informed consent form
Ethical approval
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary