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Effect of Intermittent Hepatic Inflow Occlusion During Donor Hepatectomy In Living Donor Liver Transplantation

Primary Purpose

End Stage Liver Disease, Living Donor

Status
Unknown status
Phase
Phase 3
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Intermittent hepatic inflow occlusion (IHIO)
Sponsored by
Samsung Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for End Stage Liver Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Donors and recipient of LDLT, saged ≥18 years, who will undergo LDLT with donors undergoing right hemihepatectomy and recipients receiving right hemiliver grafts
  • Informed consent agreement

Exclusion Criteria:

  • if the recipients has fulminant hepatic failure
  • if the graft to recipient body weight ratio (GRWR) is <0.9
  • if a frozen biopsy of the donor liver taken prior to donor hemihepatectomy shows >30% macrovesicular steatosis
  • if liver transplantation is ABO incompatible
  • if recipients has received previous organ transplants
  • if recipients has received or were scheduled to receive multi-organ transplants

Sites / Locations

  • Samsung Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

IHIO

Control

Arm Description

Intermittent hepatic inflow occlusion (IHIO) by clamping of the portal triad, minimizes blood loss and operation time during liver resection. In addition, ischemic preconditioning with IHIO has been reported to have protective effects in patients undergoing liver resection. IHIO'll be usually performed 3 times during donor liver parenchymal resection, with each IHIO consisting of clamping of the hepatoduodenal ligament for 15 minutes, followed by reperfusion for 5 minutes.

The donor liver parenchyma'll be transected without IHIO.

Outcomes

Primary Outcome Measures

Serum alanine aminotransferase (ALT) concentration within 5 days post-operative
The primary end-point of this study is peak serum alanine aminotransferase (ALT) concentration within 5 days post-operation on donors and recipients.

Secondary Outcome Measures

post-operative clinical courses, such as liver function tests, hospital stay, and morbidity
Secondary end-points in recipients include those involving post-operative clinical courses, such as liver function tests, graft function, stay in the intensive care unit and in-hospital mortality, hospital stay and in donors post-operative clinical courses, such as liver function tests, hospital stay and morbidity requiring additional interveition or delay of hospital stay.
Serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)- α, and hepatocyte growth factor (HGF)
Blood samples for measurement of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)- α, and hepatocyte growth factor (HGF) will be taken from donors immediately after anesthesia induction and 2 hours after graft removal, and from recipients immediately after anesthesia induction, during the anhepatic phase, 2 hours after reperfusion, and at 1 and 3 days post-operatively.
Caspase-3 and malondialdehyde in liver biopsy
Biopsy samples'll be taken from donors at the time of laparotomy, just before portal vein and hepatic artery clamping after parenchymal resection, and from recipients two hours after reperfusion. Hepatocyte injury will be determined by measuring the concentrations of caspase-3, and malondialdehyde (MDA) by ELISA.

Full Information

First Posted
July 27, 2010
Last Updated
July 27, 2010
Sponsor
Samsung Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT01171742
Brief Title
Effect of Intermittent Hepatic Inflow Occlusion During Donor Hepatectomy In Living Donor Liver Transplantation
Official Title
Effect of Intermittent Hepatic Inflow Occlusion During Donor Hepatectomy In Adult Living Donor Liver Transplantation Using Right Hemiliver Grafts
Study Type
Interventional

2. Study Status

Record Verification Date
July 2010
Overall Recruitment Status
Unknown status
Study Start Date
July 2008 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
August 2010 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor
Samsung Medical Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Intermittent hepatic inflow occlusion (IHIO), also called Pringle maneuver, is a safe and effective procedure for major hepatectomy in patients with liver disease. In addition, ischemic preconditioning with IHIO has been reported to have protective effects in patients undergoing liver resection. The role of IHIO, however, has not been fully elucidated in donors and recipients during living donor liver transplantation.
Detailed Description
Intermittent hepatic inflow occlusion (IHIO) by clamping of the portal triad, also called Pringle maneuver, is a safe and effective procedure in major hepatectomy in patients with liver disease. IHIO minimizes blood loss and operation time during liver resection. In addition, ischemic preconditioning with IHIO has been reported to have protective effects in patients undergoing liver resection. In the setting of living donor liver transplantation (LDLT), one of the most important concerns is liver donor safety. Several studies have shown the safety of IHIO in donors for liver transplantation (LT). However, the effect of preconditioning with IHIO during donor hepatectomy on LDLT recipients remains unclear. Several small series have assessed the effects on recipients of ischemic preconditioning during whole liver transplantation from deceased donors. The role of IHIO, however, has not been fully elucidated in liver donors and recipients during LDLT. In this randomized, prospective study, we'll evaluate the efficacy of IHIO in the recipients and donors.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End Stage Liver Disease, Living Donor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IHIO
Arm Type
Experimental
Arm Description
Intermittent hepatic inflow occlusion (IHIO) by clamping of the portal triad, minimizes blood loss and operation time during liver resection. In addition, ischemic preconditioning with IHIO has been reported to have protective effects in patients undergoing liver resection. IHIO'll be usually performed 3 times during donor liver parenchymal resection, with each IHIO consisting of clamping of the hepatoduodenal ligament for 15 minutes, followed by reperfusion for 5 minutes.
Arm Title
Control
Arm Type
Sham Comparator
Arm Description
The donor liver parenchyma'll be transected without IHIO.
Intervention Type
Procedure
Intervention Name(s)
Intermittent hepatic inflow occlusion (IHIO)
Intervention Description
Intermittent hepatic inflow occlusion (IHIO)'ll be usually performed 3 times during donor liver parenchymal resection, with each IHIO consisting of clamping of the hepatoduodenal ligament for 15 minutes, followed by reperfusion for 5 minutes.
Primary Outcome Measure Information:
Title
Serum alanine aminotransferase (ALT) concentration within 5 days post-operative
Description
The primary end-point of this study is peak serum alanine aminotransferase (ALT) concentration within 5 days post-operation on donors and recipients.
Time Frame
pre-operative and every day till 5 days post-operative
Secondary Outcome Measure Information:
Title
post-operative clinical courses, such as liver function tests, hospital stay, and morbidity
Description
Secondary end-points in recipients include those involving post-operative clinical courses, such as liver function tests, graft function, stay in the intensive care unit and in-hospital mortality, hospital stay and in donors post-operative clinical courses, such as liver function tests, hospital stay and morbidity requiring additional interveition or delay of hospital stay.
Time Frame
During post-operative 1 months or hospitalization
Title
Serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)- α, and hepatocyte growth factor (HGF)
Description
Blood samples for measurement of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)- α, and hepatocyte growth factor (HGF) will be taken from donors immediately after anesthesia induction and 2 hours after graft removal, and from recipients immediately after anesthesia induction, during the anhepatic phase, 2 hours after reperfusion, and at 1 and 3 days post-operatively.
Time Frame
In donors immediately after anesthesia induction and 2 hours after graft removal, and in recipients immediately after anesthesia induction, during the anhepatic phase, 2 hours after reperfusion, and at 1 and 3 days post-operatively.
Title
Caspase-3 and malondialdehyde in liver biopsy
Description
Biopsy samples'll be taken from donors at the time of laparotomy, just before portal vein and hepatic artery clamping after parenchymal resection, and from recipients two hours after reperfusion. Hepatocyte injury will be determined by measuring the concentrations of caspase-3, and malondialdehyde (MDA) by ELISA.
Time Frame
In donors at the time of laparotomy, just before portal vein and hepatic artery clamping after parenchymal resection, and in recipients two hours after reperfusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Donors and recipient of LDLT, saged ≥18 years, who will undergo LDLT with donors undergoing right hemihepatectomy and recipients receiving right hemiliver grafts Informed consent agreement Exclusion Criteria: if the recipients has fulminant hepatic failure if the graft to recipient body weight ratio (GRWR) is <0.9 if a frozen biopsy of the donor liver taken prior to donor hemihepatectomy shows >30% macrovesicular steatosis if liver transplantation is ABO incompatible if recipients has received previous organ transplants if recipients has received or were scheduled to receive multi-organ transplants
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jae-Won Joh, MD., PhD
Organizational Affiliation
Samsung Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
135-710
Country
Korea, Republic of

12. IPD Sharing Statement

Citations:
PubMed Identifier
21837746
Citation
Park JB, Joh JW, Kim SJ, Kwon CH, Chun JM, Kim JM, Moon JI, Lee SK. Effect of intermittent hepatic inflow occlusion with the Pringle maneuver during donor hepatectomy in adult living donor liver transplantation with right hemiliver grafts: a prospective, randomized controlled study. Liver Transpl. 2012 Jan;18(1):129-37. doi: 10.1002/lt.22409.
Results Reference
derived

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Effect of Intermittent Hepatic Inflow Occlusion During Donor Hepatectomy In Living Donor Liver Transplantation

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