<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/NCT03770130</url>
  </required_header>
  <id_info>
    <org_study_id>DAS-OLT Trial</org_study_id>
    <nct_id>NCT03770130</nct_id>
  </id_info>
  <brief_title>Dexmedetomidine and Liver Transplantation</brief_title>
  <official_title>Evaluation of the Impact of Dexmedetomidine on Allograft Function Recovery and Survival Following Liver Transplantation: A Randomised Control Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>RenJi Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>RenJi Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      1.1. Background 1.1.1. Perioperative ischaemia/reperfusion (I/R) injury during liver&#xD;
      transplantation is strongly associated with early allograft dysfunction, graft loss, and&#xD;
      mortality.&#xD;
&#xD;
      1.1.2. Hepatic I/R injury also causes remote damage to other organs including the renal and&#xD;
      pulmonary systems.&#xD;
&#xD;
      1.1.3. Dexmedetomidine, a selective α2-adrenoceptor agonist which is widely used as an&#xD;
      adjuvant to general anaesthesia, has been widely shown in preclinical studies to provide&#xD;
      organoprotection by ameliorating the effects of I/R injury in a range of tissues (including&#xD;
      the liver). However, prospective clinical evidence of any potential benefits in improving&#xD;
      outcomes in liver transplantation is lacking.&#xD;
&#xD;
      1.2. Objectives 1.2.1. To investigate the hypothesis that perioperative treatment with&#xD;
      dexmedetomidine reduces the incidence of early allograft dysfunction and primary graft&#xD;
      non-function in deceased donor liver transplantation.&#xD;
&#xD;
      1.2.2. The impact of dexmedetomidine on postoperative renal and pulmonary function will also&#xD;
      be examined.&#xD;
&#xD;
      1.3. Study Design This is a prospective, single-centre, randomised, parallel-group study.&#xD;
&#xD;
      1.4. Setting Departments of Anesthesiology, Renji Hosptial, Shanghai Jiao Tong University&#xD;
      School of Medicine, Shanghai, 200127, China.&#xD;
&#xD;
      1.5. Patients 200 patients (18-65 years) scheduled to undergo liver transplantation under&#xD;
      general anaesthesia.&#xD;
&#xD;
      1.6 Intervention 1.6.1. For the patients in the treatment group, a loading dose of&#xD;
      dexmedetomidine will be given after induction of anaesthesia (1μg/kg over 10 min) followed by&#xD;
      a continuous infusion (0.5μg/kg /h) until the end of surgery.&#xD;
&#xD;
      1.6.2. For patients in the placebo group, an equal volume loading dose of 0.9% saline will be&#xD;
      given after the induction of anaesthesia followed by an equal volume continuous infusion&#xD;
      until the end of surgery.&#xD;
&#xD;
      1.6.3. All other supplements, e.g. opioids, sedatives and muscle relaxant, will be identical&#xD;
      in the both arms and administered according to routine clinical practice.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 14, 2019</start_date>
  <completion_date type="Actual">December 31, 2022</completion_date>
  <primary_completion_date type="Actual">October 31, 2022</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of early allograft dysfunction (EAD) following surgery</measure>
    <time_frame>7 days</time_frame>
    <description>Defined according to Olthoff's criteria published in 2010: (1) bilirubin ≥ 10mg/dL on day 7; or (2) INR &gt; 1.6 on day 7; or (3) AST/ ALT &gt; 2000IU/L within first 7 days.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of postoperative acute kidney injury (AKI) during the postoperative day 1-7</measure>
    <time_frame>7 days</time_frame>
    <description>Defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria published in 2012: (1) Increase in serum creatinine by ≥ 0.3mg/dL within 48 hours; or (2) increase in serum creatinine to 1.5 times baseline or more within past 7 days; or (3) urine output &lt; 0.5mL/kg/h for 6 hours.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of acute respiratory distress syndrome (ARDS) during the postoperative day 1-7</measure>
    <time_frame>7 days</time_frame>
    <description>Defined according to Berlin modification of the American European Consensus Committee (AECC) definitions published in 2012: (1) Acute onset (within one week of known insult); and (2) bilateral opacities on CXR (not explained by effusions, nodules, or collapse); and (3) respiratory failure not fully explained by cardiac failure or fluid overload; and (4) Severity graded by PaO2/ FIO2 ratio with PEEP 5cmH2O i. Mild 300 ≥ PaO2/ FIO2 &gt; 200; ii. Moderate 200 ≥ PaO2/ FIO2 &gt; 100; iii. Severe 100 ≥ PaO2/ FIO2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of graft failure and retransplantation rate during 3 year follow up period.</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All cause mortality in the 3 year follow-up period.</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of primary graft non-function (PNF)</measure>
    <time_frame>30 days</time_frame>
    <description>Defined as graft loss, retransplantation, or patient death due to graft non-function in first 30 days (excluding non-function secondary to hepatic artery thrombosis, biliary complications, or recurrent hepatic disease).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">330</enrollment>
  <condition>Dexmedetomidine, Liver Transplantation, Allograft Function, Survival</condition>
  <arm_group>
    <arm_group_label>Dexmedetomidine treatment group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Anaesthesia will be maintained with sevoflurane inhalation, of which the concentration will be adjusted to maintain the BIS value between 40 and 60. Muscle relaxation will be maintained with rocuronium or cisatracurium. Analgesia will be maintained with remifentanil (administered via continuous infusion), sufentanil (administered via continuous infusion or intermittent injection), or fentanyl (administered via intermittent injection). In addition to this, patients will receive an initial loading dose of dexmedetomidine of 1μg/kg over 10 min after the induction of anaesthesia followed by a continuous infusion of 0.5μg/kg/h until the end of surgery.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Anaesthesia will be maintained with sevoflurane inhalation, of which the concentration will be adjusted to maintain the BIS value between 40 and 60. Muscle relaxation will be maintained with rocuronium or cisatracurium. Analgesia will be maintained with remifentanil (administered via continuous infusion), sufentanil (administered via continuous infusion or intermittent injection), or fentanyl (administered via intermittent injection). In addition to this, patients will receive an equal volume initial loading dose of 0.9% saline over 10 min after the induction of anaesthesia followed by an equal volume continuous infusion until the end of surgery.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexmedetomidine</intervention_name>
    <description>Dexmedetomidine, a selective α2-adrenoceptor agonist which is widely used as an adjuvant to general anaesthesia</description>
    <arm_group_label>Dexmedetomidine treatment group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline</intervention_name>
    <description>Saline, a kind of crystalloid widely used in clinical treatment</description>
    <arm_group_label>Control group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-65 years&#xD;
&#xD;
          2. Scheduled to undergo allogenic liver transplant(DCD/DBD) surgery under general&#xD;
             anaesthesia&#xD;
&#xD;
          3. Patients should meet the UCSF criteria&#xD;
&#xD;
          4. Agree to participate and give written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Severe renal dysfunction (undergoing renal replacement therapy before surgery)&#xD;
&#xD;
          2. Severe pulmonary dysfunction (including pneumonia, atelectasis, pleural effusion,&#xD;
             acute lung injury or ARDS)&#xD;
&#xD;
          3. Severe circulatory instability (severe coronary artery disease, unstable angina, left&#xD;
             ventricular ejection fraction &lt; 30%, sick sinus syndrome, severe sinus bradycardia [&lt;&#xD;
             50 bpm], second-degree or greater atrioventricular block)&#xD;
&#xD;
          4. Known allergy or intolerance to trial medication&#xD;
&#xD;
          5. Refusal to participate in the study&#xD;
&#xD;
          6. Participation in other clinical trials within 30 days prior to randomisation.&#xD;
&#xD;
          7. Retransplantation&#xD;
&#xD;
          8. Multiple organ transplantation&#xD;
&#xD;
          9. Other reasons that are considered unsuitable for study participation by the&#xD;
             responsible surgeon or anaesthetist (reasons must be documented in the case report&#xD;
             form [CRF])&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Renji Hospital, Shanghai Jiao Tong University, School of Medicine</name>
      <address>
        <city>Shanghai</city>
        <zip>200127</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>December 6, 2018</study_first_submitted>
  <study_first_submitted_qc>December 6, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 10, 2018</study_first_posted>
  <last_update_submitted>August 16, 2023</last_update_submitted>
  <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexmedetomidine</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03770130
org study id: DAS-OLT Trial
nct id: NCT03770130
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
1.1. Background 1.1.1. Perioperative ischaemia/reperfusion (I/R) injury during liver
      transplantation is strongly associated with early allograft dysfunction, graft loss, and
      mortality.

      1.1.2. Hepatic I/R injury also causes remote damage to other organs including the renal and
      pulmonary systems.

      1.1.3. Dexmedetomidine, a selective α2-adrenoceptor agonist which is widely used as an
      adjuvant to general anaesthesia, has been widely shown in preclinical studies to provide
      organoprotection by ameliorating the effects of I/R injury in a range of tissues (including
      the liver). However, prospective clinical evidence of any potential benefits in improving
      outcomes in liver transplantation is lacking.

      1.2. Objectives 1.2.1. To investigate the hypothesis that perioperative treatment with
      dexmedetomidine reduces the incidence of early allograft dysfunction and primary graft
      non-function in deceased donor liver transplantation.

      1.2.2. The impact of dexmedetomidine on postoperative renal and pulmonary function will also
      be examined.

      1.3. Study Design This is a prospective, single-centre, randomised, parallel-group study.

      1.4. Setting Departments of Anesthesiology, Renji Hosptial, Shanghai Jiao Tong University
      School of Medicine, Shanghai, 200127, China.

      1.5. Patients 200 patients (18-65 years) scheduled to undergo liver transplantation under
      general anaesthesia.

      1.6 Intervention 1.6.1. For the patients in the treatment group, a loading dose of
      dexmedetomidine will be given after induction of anaesthesia (1μg/kg over 10 min) followed by
      a continuous infusion (0.5μg/kg /h) until the end of surgery.

      1.6.2. For patients in the placebo group, an equal volume loading dose of 0.9% saline will be
      given after the induction of anaesthesia followed by an equal volume continuous infusion
      until the end of surgery.

      1.6.3. All other supplements, e.g. opioids, sedatives and muscle relaxant, will be identical
      in the both arms and administered according to routine clinical practice.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Incidence of early allograft dysfunction (EAD) following surgery
time frame: 7 days
description: Defined according to Olthoff's criteria published in 2010: (1) bilirubin ≥ 10mg/dL on day 7; or (2) INR > 1.6 on day 7; or (3) AST/ ALT > 2000IU/L within first 7 days.
measure: Incidence of postoperative acute kidney injury (AKI) during the postoperative day 1-7
time frame: 7 days
description: Defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria published in 2012: (1) Increase in serum creatinine by ≥ 0.3mg/dL within 48 hours; or (2) increase in serum creatinine to 1.5 times baseline or more within past 7 days; or (3) urine output < 0.5mL/kg/h for 6 hours.
measure: Incidence of acute respiratory distress syndrome (ARDS) during the postoperative day 1-7
time frame: 7 days
description: Defined according to Berlin modification of the American European Consensus Committee (AECC) definitions published in 2012: (1) Acute onset (within one week of known insult); and (2) bilateral opacities on CXR (not explained by effusions, nodules, or collapse); and (3) respiratory failure not fully explained by cardiac failure or fluid overload; and (4) Severity graded by PaO2/ FIO2 ratio with PEEP 5cmH2O i. Mild 300 ≥ PaO2/ FIO2 > 200; ii. Moderate 200 ≥ PaO2/ FIO2 > 100; iii. Severe 100 ≥ PaO2/ FIO2.
measure: Incidence of graft failure and retransplantation rate during 3 year follow up period.
time frame: 3 years
measure: All cause mortality in the 3 year follow-up period.
time frame: 3 years
measure: Incidence of primary graft non-function (PNF)
time frame: 30 days
description: Defined as graft loss, retransplantation, or patient death due to graft non-function in first 30 days (excluding non-function secondary to hepatic artery thrombosis, biliary complications, or recurrent hepatic disease).
arm group label: Dexmedetomidine treatment group
arm group type: Experimental
description: Anaesthesia will be maintained with sevoflurane inhalation, of which the concentration will be adjusted to maintain the BIS value between 40 and 60. Muscle relaxation will be maintained with rocuronium or cisatracurium. Analgesia will be maintained with remifentanil (administered via continuous infusion), sufentanil (administered via continuous infusion or intermittent injection), or fentanyl (administered via intermittent injection). In addition to this, patients will receive an initial loading dose of dexmedetomidine of 1μg/kg over 10 min after the induction of anaesthesia followed by a continuous infusion of 0.5μg/kg/h until the end of surgery.
arm group label: Control group
arm group type: Placebo Comparator
description: Anaesthesia will be maintained with sevoflurane inhalation, of which the concentration will be adjusted to maintain the BIS value between 40 and 60. Muscle relaxation will be maintained with rocuronium or cisatracurium. Analgesia will be maintained with remifentanil (administered via continuous infusion), sufentanil (administered via continuous infusion or intermittent injection), or fentanyl (administered via intermittent injection). In addition to this, patients will receive an equal volume initial loading dose of 0.9% saline over 10 min after the induction of anaesthesia followed by an equal volume continuous infusion until the end of surgery.
intervention type: Drug
intervention name: Dexmedetomidine
description: Dexmedetomidine, a selective α2-adrenoceptor agonist which is widely used as an adjuvant to general anaesthesia
arm group label: Dexmedetomidine treatment group
intervention type: Drug
intervention name: Saline
description: Saline, a kind of crystalloid widely used in clinical treatment
arm group label: Control group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
mesh term: Dexmedetomidine