<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03758352</url>
  </required_header>
  <id_info>
    <org_study_id>TRSPLNT001</org_study_id>
    <nct_id>NCT03758352</nct_id>
  </id_info>
  <brief_title>The Effect of Remote Ischemic Preconditioning on Ischemia/Reperfusion Injury in a Liver Transplant Recipient</brief_title>
  <official_title>The Effect of Remote Ischemic Preconditioning on Ischemia/Reperfusion Injury in a Liver Transplant Recipient (TRSPLNT) - A Randomized, Controlled, Double-blinded Clinical Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rigshospitalet, Denmark</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rigshospitalet, Denmark</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Ischemia and reperfusion injury is unavoidable during a liver transplantation. Remote&#xD;
      ischemic preconditioning, a safe and feasible method, has previously been shown to reduce&#xD;
      ischemia and reperfusion injury. In the transplantation setting, focus of remote ischemic&#xD;
      preconditioning has been on the donor. However, preconditioning of the recipient may be a&#xD;
      better approach due to the mechanisms by which ischemic preconditioning protects against&#xD;
      ischemia and reperfusion injury.&#xD;
&#xD;
      The aim of this randomised, double-blinded clinical trial is to biochemically assess the&#xD;
      liver function after application of remote ischemic preconditioning on the recipient.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background The use of solid organ transplantation, including liver transplantation, is the&#xD;
      golden standard for many end-stage solid organ diseases. Ischemia and reperfusion injury is&#xD;
      unavoidable during a liver transplantation. Remote ischemic preconditioning, a safe and&#xD;
      feasible method, has previously been shown to reduce ischemia and reperfusion injury. This&#xD;
      may have a similar effect in a liver transplantation setting. In the transplantation setting,&#xD;
      focus of remote ischemic preconditioning has been on the donor. However, preconditioning of&#xD;
      the recipient may be a better approach due to the mechanisms by which ischemic&#xD;
      preconditioning protects against ischemia and reperfusion injury.&#xD;
&#xD;
      The aim of this randomised, double-blinded clinical trial is to biochemically assess the&#xD;
      liver function after application of remote ischemic preconditioning on the recipient.&#xD;
&#xD;
      Methods 52 patients undergoing a liver transplantation, included in accordance to the&#xD;
      inclusion criteria, will be allocated to an intervention group (rIC-group) and compared to a&#xD;
      retrospective non-intervention control group (non-rIC group) consisting of 52 patients.&#xD;
      Patients in the non-intervention group will also be included in accordance to the inclusion&#xD;
      criteria. Within two hours before surgery, patients in the intervention group will be&#xD;
      subjected to four rounds of five-minute inflations and five-minute deflations of a pneumatic&#xD;
      tourniquet applied on the right leg.&#xD;
&#xD;
      Follow-up time will be 30 days.&#xD;
&#xD;
      Measurements The aim of this trial is to assess the effect of remote ischemic preconditioning&#xD;
      on the extent of liver injury and inflammation as a result of ischemia and reperfusion&#xD;
      injury. Assessment will be done by measurement of biomarkers relevant to liver function and&#xD;
      liver injury.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Large sample size&#xD;
  </why_stopped>
  <start_date type="Anticipated">April 2020</start_date>
  <completion_date type="Anticipated">November 2022</completion_date>
  <primary_completion_date type="Anticipated">June 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Patients will be allocated to an intervention group (rIC) and compared to a retrospective control group. Data assessment will be blinded to the assessor.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
    <masking_description>The patient enrolment will be done by the on-call doctor and intervention will be performed by unblinded research personnel who won't be involved in sample collection or data analysis.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Post-operative change in ALT</measure>
    <time_frame>Day 0-4</time_frame>
    <description>Extent of liver injury measured as change in ALT postoperative from day zero to day four .</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Post-operative change in Aspartate Amonitransferase</measure>
    <time_frame>Day 0-4</time_frame>
    <description>Serological markers of liver function</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-operative change in Bilirubin</measure>
    <time_frame>Day 0-4</time_frame>
    <description>Serological markers of liver function</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-operative change in Alkaline Phosphatase</measure>
    <time_frame>Day 0-4</time_frame>
    <description>Serological markers of liver function</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-operative change in International Normalised Ratio</measure>
    <time_frame>Day 0-4</time_frame>
    <description>Serological markers of liver function</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Complication rate</measure>
    <time_frame>Follow-up on day 30</time_frame>
    <description>Rate of post-operative complications</description>
  </other_outcome>
  <other_outcome>
    <measure>Days in ICU (Intensive Care Unit)</measure>
    <time_frame>Follow-up on day 30</time_frame>
    <description>Length of post-operative stay in ICU</description>
  </other_outcome>
  <other_outcome>
    <measure>Total length of hospital-stay</measure>
    <time_frame>Follow-up on day 30</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Liver Transplant; Complications</condition>
  <condition>Ischemia Reperfusion Injury</condition>
  <arm_group>
    <arm_group_label>intervention group (rIC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The rIC procedure will be applied on seated patients, who have been resting for at least five minutes. The active rIC procedure consists of four five-minute inflations of a pneumatic tourniquet to 100 mmHg above the patient's systolic blood pressure separated by five-minute periods of complete deflation. Placement of the pneumatic tourniquet will be unilaterally on a lower limb (right thigh)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>control group (non-rIC)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>The control group will be a retrospective group, who have undergone a liver transplantation and meet the inclusion criteria.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>remote ischemic preconditioning (rIC)</intervention_name>
    <description>Short intermittent peripheral occlusions and reperfusions of the blood flow in the right lower extremity with the help of a tourniquet.</description>
    <arm_group_label>intervention group (rIC)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>non remote ischemic preconditioning (non-rIC)</intervention_name>
    <description>Retrospective group who have not undergone intervention.</description>
    <arm_group_label>control group (non-rIC)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients undergoing liver transplantation&#xD;
&#xD;
          -  Patients aged 18 or above&#xD;
&#xD;
          -  Patients who have given an informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients undergoing re-transplantation.&#xD;
&#xD;
          -  Patients who do not or cannot give an informed consent.&#xD;
&#xD;
          -  Patients who have undergone surgery six weeks prior to liver transplantation.&#xD;
&#xD;
          -  Patients with known peripheral vascular disease.&#xD;
&#xD;
          -  Patients with an infection localized to the area of rIC-intervention&#xD;
&#xD;
          -  Patients with at a high risk or with previous history of multiple thrombo-embolic&#xD;
             diseases.&#xD;
&#xD;
          -  Patients undergoing active immunosuppressive therapy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Waqas Farooqui, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Doctor</affiliation>
  </overall_official>
  <reference>
    <citation>Farooqui W, Pommergaard HC, Rasmussen A. Remote ischemic preconditioning of transplant recipients to reduce graft ischemia and reperfusion injuries: A systematic review. Transplant Rev (Orlando). 2018 Jan;32(1):10-15. doi: 10.1016/j.trre.2017.06.001. Epub 2017 Jun 15.</citation>
    <PMID>28637593</PMID>
  </reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>November 25, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>October 5, 2020</last_update_submitted>
  <last_update_submitted_qc>October 5, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 8, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Rigshospitalet, Denmark</investigator_affiliation>
    <investigator_full_name>Waqas Farooqui</investigator_full_name>
    <investigator_title>MD, Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>ischemia reperfusion injury</keyword>
  <keyword>remote ischemic preconditioning</keyword>
  <keyword>liver transplantation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Reperfusion Injury</mesh_term>
    <mesh_term>Ischemia</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03758352
org study id: TRSPLNT001
nct id: NCT03758352
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Ischemia and reperfusion injury is unavoidable during a liver transplantation. Remote
      ischemic preconditioning, a safe and feasible method, has previously been shown to reduce
      ischemia and reperfusion injury. In the transplantation setting, focus of remote ischemic
      preconditioning has been on the donor. However, preconditioning of the recipient may be a
      better approach due to the mechanisms by which ischemic preconditioning protects against
      ischemia and reperfusion injury.

      The aim of this randomised, double-blinded clinical trial is to biochemically assess the
      liver function after application of remote ischemic preconditioning on the recipient.
Background The use of solid organ transplantation, including liver transplantation, is the
      golden standard for many end-stage solid organ diseases. Ischemia and reperfusion injury is
      unavoidable during a liver transplantation. Remote ischemic preconditioning, a safe and
      feasible method, has previously been shown to reduce ischemia and reperfusion injury. This
      may have a similar effect in a liver transplantation setting. In the transplantation setting,
      focus of remote ischemic preconditioning has been on the donor. However, preconditioning of
      the recipient may be a better approach due to the mechanisms by which ischemic
      preconditioning protects against ischemia and reperfusion injury.

      The aim of this randomised, double-blinded clinical trial is to biochemically assess the
      liver function after application of remote ischemic preconditioning on the recipient.

      Methods 52 patients undergoing a liver transplantation, included in accordance to the
      inclusion criteria, will be allocated to an intervention group (rIC-group) and compared to a
      retrospective non-intervention control group (non-rIC group) consisting of 52 patients.
      Patients in the non-intervention group will also be included in accordance to the inclusion
      criteria. Within two hours before surgery, patients in the intervention group will be
      subjected to four rounds of five-minute inflations and five-minute deflations of a pneumatic
      tourniquet applied on the right leg.

      Follow-up time will be 30 days.

      Measurements The aim of this trial is to assess the effect of remote ischemic preconditioning
      on the extent of liver injury and inflammation as a result of ischemia and reperfusion
      injury. Assessment will be done by measurement of biomarkers relevant to liver function and
      liver injury.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Patients will be allocated to an intervention group (rIC) and compared to a retrospective control group. Data assessment will be blinded to the assessor.
primary purpose: Prevention
masking: Double (Investigator, Outcomes Assessor)
masking description: The patient enrolment will be done by the on-call doctor and intervention will be performed by unblinded research personnel who won't be involved in sample collection or data analysis.
measure: Post-operative change in ALT
time frame: Day 0-4
description: Extent of liver injury measured as change in ALT postoperative from day zero to day four .
measure: Post-operative change in Aspartate Amonitransferase
time frame: Day 0-4
description: Serological markers of liver function
measure: Post-operative change in Bilirubin
time frame: Day 0-4
description: Serological markers of liver function
measure: Post-operative change in Alkaline Phosphatase
time frame: Day 0-4
description: Serological markers of liver function
measure: Post-operative change in International Normalised Ratio
time frame: Day 0-4
description: Serological markers of liver function
measure: Complication rate
time frame: Follow-up on day 30
description: Rate of post-operative complications
measure: Days in ICU (Intensive Care Unit)
time frame: Follow-up on day 30
description: Length of post-operative stay in ICU
measure: Total length of hospital-stay
time frame: Follow-up on day 30
arm group label: intervention group (rIC)
arm group type: Experimental
description: The rIC procedure will be applied on seated patients, who have been resting for at least five minutes. The active rIC procedure consists of four five-minute inflations of a pneumatic tourniquet to 100 mmHg above the patient's systolic blood pressure separated by five-minute periods of complete deflation. Placement of the pneumatic tourniquet will be unilaterally on a lower limb (right thigh)
arm group label: control group (non-rIC)
arm group type: Other
description: The control group will be a retrospective group, who have undergone a liver transplantation and meet the inclusion criteria.
intervention type: Procedure
intervention name: remote ischemic preconditioning (rIC)
description: Short intermittent peripheral occlusions and reperfusions of the blood flow in the right lower extremity with the help of a tourniquet.
arm group label: intervention group (rIC)
intervention type: Other
intervention name: non remote ischemic preconditioning (non-rIC)
description: Retrospective group who have not undergone intervention.
arm group label: control group (non-rIC)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Waqas Farooqui, MD
role: Principal Investigator
affiliation: Doctor
citation: Farooqui W, Pommergaard HC, Rasmussen A. Remote ischemic preconditioning of transplant recipients to reduce graft ischemia and reperfusion injuries: A systematic review. Transplant Rev (Orlando). 2018 Jan;32(1):10-15. doi: 10.1016/j.trre.2017.06.001. Epub 2017 Jun 15.
PMID: 28637593
responsible party type: Principal Investigator
investigator affiliation: Rigshospitalet, Denmark
investigator full name: Waqas Farooqui
investigator title: MD, Principal Investigator
mesh term: Reperfusion Injury
mesh term: Ischemia
mesh term: Wounds and Injuries
sharing ipd: Undecided