Clincosm LogoSign in Get a demo

The Effect of Remote Ischemic Preconditioning in Living Donor Hepatectomy

Sponsor
Asan Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT03386435
Collaborator
(none)
160
Enrollment
1
Location
2
Arms
14.3
Actual Duration (Months)
11.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Liver transplantation is the gold standard treatment for patients with end-stage liver disease. Despite its outstanding success, liver transplantation still entails certain complications including ischemia-reperfusion injury. Remote ischemic preconditioning is a novel and simple therapeutic method to lessen the harmful effects of ischemia-reperfusion injury, however, the majority of remote ischemic preconditioning studies on hepatic ischemia-reperfusion injury have been animal studies. Therefore, our aim was to assess the effects of remote ischemic preconditioning on postoperative liver function in living donor hepatectomy.

Condition or Disease Intervention/Treatment Phase
  • Procedure: remote ischemic preconditioning
 N/A

Detailed Description

Liver transplantation(LT) is the gold standard treatment for patients with end-stage liver disease. In light of advancements in surgical techniques, immunosuppressive agents, and perioperative critical care, the overall 3-year survival of patients undergoing LT has exceeded 80%. Despite its outstanding success, LT still entails certain complications including ischemia-reperfusion injury (IRI).

IRI occurs when the blood supply to an organ or tissue is temporarily cut-off and then restored, and it is well-known as an underlying cause of primary non-function, biliary complications, and eventual graft loss after LT. Despite many attempts to ameliorate hepatic IRI, no definitive therapies have been established. In addition, the mechanisms of IRI remain largely unclear.

Remote ischemic preconditioning (RIPC) is a novel and simple therapeutic method to lessen the harmful effects of IRI. RIPC indicate that brief episodes of ischemia with intermittent reperfusion are introduced at a remote site, leading to systemic protection against subsequent insults as evinced on kidney, heart, liver, and other tissues. While RIPC has been shown to reduce hepatic IRI in several small animal studies, the beneficial effects of RIPC in hepatic IRI have been inconsistent. By far, the majority of RIPC studies on hepatic IRI have been animal studies; hence, there are limitations relating to the lack of human clinical trials.

Therefore, our aim was to assess the effects of RIPC on postoperative liver function in living donor hepatectomy.

Study Design

Study Type:
Interventional
Actual Enrollment :
160 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
study group : remote ischemic preconditioning control group : nonestudy group : remote ischemic preconditioning control group : none
Masking:
Double (Participant, Investigator)
Primary Purpose:
Prevention
Official Title:
The Effect of Remote Ischemic Preconditioning on the Postoperative Liver Function in Living Donor Hepatectomy: a Randomized Clinical Trial
Actual Study Start Date :
Aug 22, 2016
Actual Primary Completion Date :
Aug 31, 2017
Actual Study Completion Date :
Oct 30, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: RIPC

intervention: RIPC groups receive remote ischaemic preconditioning after anaesthesia induction and before surgery started.

Procedure: remote ischemic preconditioning
Remote ischemic preconditioning was performed following anesthesia induction in donors. The protocol involves 3 cycles of 5-minute inflation of a blood pressure cuff to 200 mm Hg to one upper arm, followed by 5-minute reperfusion with the cuff deflated
Other Names:
  • RIPC

    		•
    No Intervention: Control

    In the control group, the same maneuver was applied but without cuff inflation.

    Outcome Measures

    Primary Outcome Measures

    1. Postopera The Maximal Aspartate Aminotransferase Level Within 7 Postoperative Days [within 7 days after operation]

      The serial assessments of routine laboratory values were used as early markers for postoperative liver function. The maximal aspartate aminotransferase level within 7 postoperative days were assessed following RIPC in living donor hepatectomy.

    2. The Maximal Alanine Aminotransferase Level Within 7 Postoperative Days [within 7 days after operation]

      The serial assessments of routine laboratory values were used as early markers for postoperative liver function. The maximal alanine aminotransferase level within 7 postoperative days were assessed following RIPC in living donor hepatectomy

    Secondary Outcome Measures

    1. Number of Participants With Delayed Recovery of Liver Function [postoperative 7 days]

      The incidence of delayed recovery of hepatic function (DRHF) were used as surrogate parameters indicating the possible benefits of RIPC. DRHF was defined based on a proposal by the International Study Group of Liver Surgery, as follows: an impaired ability of the liver to maintain its synthetic, excretory, and detoxifying functions, which are characterized by an increased PT INR and concomitant hyperbilirubinemia (considering the normal limits of the local laboratory) on or after postoperative day 5. The normal upper limits of PT and bilirubin in our institutional laboratory were 1.30 INR and 1.2 mg/dL, respectively. If either the PT INR or serum bilirubin concentration was preoperatively elevated, DRHF was defined by an increasing PT INR and increasing serum bilirubin concentration on or after postoperative day 5 (compared with the values of the previous day).

    2. Postoperative Liver Regeneration [1 month]

      The postoperative liver regeneration index (LRI) at postoperative 1 month ) was used as surrogate parameters indicating the possible benefits of RIPC. The LRI was defined as [(VLR - VFLR)/VFLR)] × 100, where VLR is the volume of the liver remnant and VFLR is the volume of the future liver remnant. Liver volume was calculated by CT volumetry using 3-mm-thick dynamic CT images. The graft weight was subtracted from the total liver volume to define the future liver remnant.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Donors who plan to have living right hepatectomy for liver transplantation.

    • age : between 18 to 60 years.

    Exclusion Criteria:

    • donors who plan to donate left lobe

    • donors who plan to have laparoscopic right hepatectomy

    • donors who cannot proceed remote ischemic preconditioning

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Asan medical center Seoul Songpa-gu Korea, Republic of 05505

    Sponsors and Collaborators

    • Asan Medical Center

    Investigators

    • Principal Investigator: Jun-Gol Song, Ph.D., Asan Medical Center

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Jun-Gol Song, Associate Professor, Asan Medical Center
    ClinicalTrials.gov Identifier:
    NCT03386435
    Other Study ID Numbers:
    • RIPC_donor
    First Posted:
    Dec 29, 2017
    Last Update Posted:
    Aug 19, 2019
    Last Verified:
    Aug 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Jun-Gol Song, Associate Professor, Asan Medical Center
    remote ischemic preconditioning
    liver donors
    Additional relevant MeSH terms:
    Reperfusion Injury
    Ischemia

    Study Results

    Participant Flow

    Recruitment Details For the donor group, adult (aged 18-60 years) liver donors scheduled for elective donor right hepatectomy from August 2016 to July 2017 at Asan Medical Center in Seoul, Korea, were screened for eligibility.
    Pre-assignment Detail
    Arm/Group Title RIPC Group Control Group
    Arm/Group Description received remote ischemic preconditioning remote ischemic preconditioning: transient brief episodes of ischemia at a remote site before a subsequent prolonged ischemia/reperfusion injury of the target organ no intervention
    Period Title: Overall Study
    STARTED 80 80
    COMPLETED 75 73
    NOT COMPLETED 5 7

    Baseline Characteristics

    Arm/Group Title RIPC Control Total
    Arm/Group Description intervention: RIPC groups receive remote ischaemic preconditioning after anaesthesia induction and before surgery started. remote ischemic preconditioning: Remote ischemic preconditioning was performed following anesthesia induction in donors. The protocol involves 3 cycles of 5-minute inflation of a blood pressure cuff to 200 mm Hg to one upper arm, followed by 5-minute reperfusion with the cuff deflated In the control group, the same maneuver was applied but without cuff inflation. Total of all reporting groups
    Overall Participants 75 73 148
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    75
    100%
    73
    100%
    148
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    21
    28%
    22
    30.1%
    43
    29.1%
    Male
    54
    72%
    51
    69.9%
    105
    70.9%
    Race/Ethnicity, Customized (Count of Participants)
    Asian
    75
    100%
    73
    100%
    148
    100%
    Region of Enrollment (Count of Participants)
    South Korea
    75
    100%
    73
    100%
    148
    100%
    Body mass index (kg/m^2) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [kg/m^2]
    23.7
    (2.6)
    24.1
    (2.7)
    23.9
    (2.7)

    Outcome Measures

    1. Primary Outcome
    Title Postopera The Maximal Aspartate Aminotransferase Level Within 7 Postoperative Days
    Description The serial assessments of routine laboratory values were used as early markers for postoperative liver function. The maximal aspartate aminotransferase level within 7 postoperative days were assessed following RIPC in living donor hepatectomy.
    Time Frame within 7 days after operation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title RIPC Control
    Arm/Group Description intervention: RIPC groups receive remote ischaemic preconditioning after anaesthesia induction and before surgery started. remote ischemic preconditioning: Remote ischemic preconditioning was performed following anesthesia induction in donors. The protocol involves 3 cycles of 5-minute inflation of a blood pressure cuff to 200 mm Hg to one upper arm, followed by 5-minute reperfusion with the cuff deflated In the control group, the same maneuver was applied but without cuff inflation.
    Measure Participants 75 73
    Mean (Inter-Quartile Range) [IU/L]
    145
    152
    2. Primary Outcome
    Title The Maximal Alanine Aminotransferase Level Within 7 Postoperative Days
    Description The serial assessments of routine laboratory values were used as early markers for postoperative liver function. The maximal alanine aminotransferase level within 7 postoperative days were assessed following RIPC in living donor hepatectomy
    Time Frame within 7 days after operation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title RIPC Control
    Arm/Group Description intervention: RIPC groups receive remote ischaemic preconditioning after anaesthesia induction and before surgery started. remote ischemic preconditioning: Remote ischemic preconditioning was performed following anesthesia induction in donors. The protocol involves 3 cycles of 5-minute inflation of a blood pressure cuff to 200 mm Hg to one upper arm, followed by 5-minute reperfusion with the cuff deflated In the control group, the same maneuver was applied but without cuff inflation.
    Measure Participants 75 73
    Mean (Inter-Quartile Range) [IU/L]
    148
    152
    3. Secondary Outcome
    Title Number of Participants With Delayed Recovery of Liver Function
    Description The incidence of delayed recovery of hepatic function (DRHF) were used as surrogate parameters indicating the possible benefits of RIPC. DRHF was defined based on a proposal by the International Study Group of Liver Surgery, as follows: an impaired ability of the liver to maintain its synthetic, excretory, and detoxifying functions, which are characterized by an increased PT INR and concomitant hyperbilirubinemia (considering the normal limits of the local laboratory) on or after postoperative day 5. The normal upper limits of PT and bilirubin in our institutional laboratory were 1.30 INR and 1.2 mg/dL, respectively. If either the PT INR or serum bilirubin concentration was preoperatively elevated, DRHF was defined by an increasing PT INR and increasing serum bilirubin concentration on or after postoperative day 5 (compared with the values of the previous day).
    Time Frame postoperative 7 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title RIPC Control
    Arm/Group Description intervention: RIPC groups receive remote ischaemic preconditioning after anaesthesia induction and before surgery started. remote ischemic preconditioning: Remote ischemic preconditioning was performed following anesthesia induction in donors. The protocol involves 3 cycles of 5-minute inflation of a blood pressure cuff to 200 mm Hg to one upper arm, followed by 5-minute reperfusion with the cuff deflated In the control group, the same maneuver was applied but without cuff inflation.
    Measure Participants 75 73
    Count of Participants [Participants]
    5
    6.7%
    0
    0%
    4. Secondary Outcome
    Title Postoperative Liver Regeneration
    Description The postoperative liver regeneration index (LRI) at postoperative 1 month ) was used as surrogate parameters indicating the possible benefits of RIPC. The LRI was defined as [(VLR - VFLR)/VFLR)] × 100, where VLR is the volume of the liver remnant and VFLR is the volume of the future liver remnant. Liver volume was calculated by CT volumetry using 3-mm-thick dynamic CT images. The graft weight was subtracted from the total liver volume to define the future liver remnant.
    Time Frame 1 month

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title RIPC Control
    Arm/Group Description intervention: RIPC groups receive remote ischaemic preconditioning after anaesthesia induction and before surgery started. remote ischemic preconditioning: Remote ischemic preconditioning was performed following anesthesia induction in donors. The protocol involves 3 cycles of 5-minute inflation of a blood pressure cuff to 200 mm Hg to one upper arm, followed by 5-minute reperfusion with the cuff deflated In the control group, the same maneuver was applied but without cuff inflation.
    Measure Participants 75 73
    Mean (Inter-Quartile Range) [percentage of liver volume]
    83.3
    94.9

    Adverse Events

    Time Frame 1 year
    Adverse Event Reporting Description
    Arm/Group Title RIPC Control
    Arm/Group Description intervention: RIPC groups receive remote ischaemic preconditioning after anaesthesia induction and before surgery started. remote ischemic preconditioning: Remote ischemic preconditioning was performed following anesthesia induction in donors. The protocol involves 3 cycles of 5-minute inflation of a blood pressure cuff to 200 mm Hg to one upper arm, followed by 5-minute reperfusion with the cuff deflated In the control group, the same maneuver was applied but without cuff inflation.
    All Cause Mortality
    RIPC Control
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/75 (0%) 0/73 (0%)
    Serious Adverse Events
    RIPC Control
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/75 (0%) 0/73 (0%)
    Other (Not Including Serious) Adverse Events
    RIPC Control
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/75 (0%) 0/73 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Jun-Gol Song, MD, PhD
    Organization Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
    Phone +82-2-3010-3869
    Email jungol.song@amc.seoul.kr
    Responsible Party:
    Jun-Gol Song, Associate Professor, Asan Medical Center
    ClinicalTrials.gov Identifier:
    NCT03386435
    Other Study ID Numbers:
    • RIPC_donor
    First Posted:
    Dec 29, 2017
    Last Update Posted:
    Aug 19, 2019
    Last Verified:
    Aug 1, 2019