<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/NCT01735591</url>
  </required_header>
  <id_info>
    <org_study_id>1WB/3DG1</org_study_id>
    <nct_id>NCT01735591</nct_id>
  </id_info>
  <brief_title>Administration of Probiotics in Cirrhotic Patients Listed for Liver Transplantation</brief_title>
  <official_title>An Attempt to Optimize the Results of Liver Transplantation With Administration of Probiotics.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Warsaw</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministry of Science and Higher Education, Poland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Medical University of Warsaw</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study was to evaluate the impact of the administration of probiotics on&#xD;
      outcomes of patients qualified for liver transplantation, both in the pre-transplant period&#xD;
      and in the early postoperative period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Gut microflora plays an important role in the pathogenesis of complications of liver&#xD;
      cirrhosis, mainly due to microbial translocation. According to several studies,&#xD;
      administration of probiotics in patients with cirrhosis has positive effect on minimal&#xD;
      hepatic encephalopathy. The aim of this study was to evaluate the impact of probiotics&#xD;
      administration on outcomes of patients qualified for liver transplantation, both in the&#xD;
      pre-transplant period and in the early postoperative period. This study will be performed on&#xD;
      200 patients randomized into the probiotic and placebo groups. Daily administration of either&#xD;
      probiotics or placebo will be continued from the date of inclusion in the study until the&#xD;
      date of liver transplantation. A quantitative and qualitative analyses of faecal microflora&#xD;
      will be performed in each patient before and after 10 week period (or shorter, depending on&#xD;
      the time on the waiting list) of administration of either probiotic or placebo.&#xD;
      Microbiological analyses of air samples from patients' home environment will be performed in&#xD;
      each case. Both groups of patients will be compared with respect to primary and secondary&#xD;
      outcome measures.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">November 2015</completion_date>
  <primary_completion_date type="Actual">November 2015</primary_completion_date>
  <phase>N/A</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>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>All-cause postoperative mortality</measure>
    <time_frame>90 days after the date of liver transplantation</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Postoperative infection</measure>
    <time_frame>30 days from the date of liver transplantation</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mortality on the waiting list</measure>
    <time_frame>From the date of inclusion until the date of liver transplantation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infections in the pre-transplantation period</measure>
    <time_frame>From the date of inclusion until the date of transplantation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Primary non-function after liver transplantation</measure>
    <time_frame>14 days after the date of liver transplantation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in model for end-stage liver disease score</measure>
    <time_frame>From the date of inclusion until the date of transplantation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Child-Turcotte-Pugh class</measure>
    <time_frame>From the date of inclusion until the date of transplantation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of hospital admissions due to infections in the pre-transplantation period</measure>
    <time_frame>From the date of inclusion until the date of transplantation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of hospital admission due to complications of liver cirrhosis in the pre-transplantation period</measure>
    <time_frame>From the date of inclusion until the date of transplantation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum activity of transaminases on the first 5 postoperative days</measure>
    <time_frame>5 days after the date of liver transplantation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum bilirubin concentration in the first 5 postoperative days</measure>
    <time_frame>5 days after the date of liver transplantation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>International normalized ratio values during the first 5 postoperative days</measure>
    <time_frame>5 days after the date of liver transplantation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in model for end-stage liver disease score in the pre-transplantation period</measure>
    <time_frame>10 weeks</time_frame>
    <description>To be assessed if the period between inclusion in the study and liver transplantation would not be shorter than 10 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Chil-Turcotte-Pugh class in the pre-transplantation period</measure>
    <time_frame>10 weeks</time_frame>
    <description>To be assessed if the period between inclusion in the study and liver transplantation would not be shorter than 10 weeks</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Changes in faecal microflora</measure>
    <time_frame>10 weeks</time_frame>
    <description>Differences in the number of colony forming units in 1 g of stool for particular bacterial and fungal species after 10 weeks of probiotic/placebo administration</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">55</enrollment>
  <condition>Liver Cirrhosis</condition>
  <arm_group>
    <arm_group_label>Probiotic</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Capsules with 3x10^9 colony forming units (Lactococcus lactis PB 411 - 50%; Lactobacillus casei PB 121 - 25%; Lactobacillus acidophilus PB 111 - 12,5%; Bifidobacterium bifidum PB 211 - 12,5%). 1 capsule a day from inclusion until liver transplantation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo, 1 capsule a day from inclusion until the date of liver transplantation</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo, 1 capsule a day from inclusion until the date of liver transplantation</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Probiotic</intervention_name>
    <description>Capsules with 3x10^9 colony forming units of: Lactococcus lactis PB 411 (50%), Lactobacillus casei PB 121 (25%), Lactobacillus acidophilus PB 111 (12,5%), Bifidobacterium bifidum PB 211 (12,5)</description>
    <arm_group_label>Probiotic</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Liver cirrhosis&#xD;
&#xD;
          -  Active status on the waiting list for liver transplantation&#xD;
&#xD;
          -  Confirmed etiology of liver disease&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Malignancy&#xD;
&#xD;
          -  Human Immunodeficiency Virus infection&#xD;
&#xD;
          -  Immunosuppressive treatment prior to liver transplantation&#xD;
&#xD;
          -  Cystic fibrosis&#xD;
&#xD;
          -  Creatinine clearance rate &lt; 50 mL/min&#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>Michał Grąt, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of Warsaw, Department of General, Transplant and Liver Surgery</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Marek Krawczyk, Professor</last_name>
    <role>Study Chair</role>
    <affiliation>Medical University of Warsaw, Department of General, Transplant and Liver Surgery</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of General, Transplant and Liver Surgery, Medical University of Warsaw</name>
      <address>
        <city>Warsaw</city>
        <state>Mazowieckie</state>
        <zip>02-097</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Poland</country>
  </location_countries>
  <verification_date>November 2015</verification_date>
  <study_first_submitted>November 23, 2012</study_first_submitted>
  <study_first_submitted_qc>November 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2012</study_first_posted>
  <last_update_submitted>July 28, 2016</last_update_submitted>
  <last_update_submitted_qc>July 28, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 29, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Liver cirrhosis</keyword>
  <keyword>Liver transplantation</keyword>
  <keyword>Probiotics</keyword>
  <keyword>Mortality</keyword>
  <keyword>Liver function</keyword>
  <keyword>Infections</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_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/NCT01735591
org study id: 1WB/3DG1
nct id: NCT01735591
lead sponsor: 
collaborator: 
has dmc: Yes
The aim of this study was to evaluate the impact of the administration of probiotics on
      outcomes of patients qualified for liver transplantation, both in the pre-transplant period
      and in the early postoperative period.
Gut microflora plays an important role in the pathogenesis of complications of liver
      cirrhosis, mainly due to microbial translocation. According to several studies,
      administration of probiotics in patients with cirrhosis has positive effect on minimal
      hepatic encephalopathy. The aim of this study was to evaluate the impact of probiotics
      administration on outcomes of patients qualified for liver transplantation, both in the
      pre-transplant period and in the early postoperative period. This study will be performed on
      200 patients randomized into the probiotic and placebo groups. Daily administration of either
      probiotics or placebo will be continued from the date of inclusion in the study until the
      date of liver transplantation. A quantitative and qualitative analyses of faecal microflora
      will be performed in each patient before and after 10 week period (or shorter, depending on
      the time on the waiting list) of administration of either probiotic or placebo.
      Microbiological analyses of air samples from patients' home environment will be performed in
      each case. Both groups of patients will be compared with respect to primary and secondary
      outcome measures.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: All-cause postoperative mortality
time frame: 90 days after the date of liver transplantation
measure: Postoperative infection
time frame: 30 days from the date of liver transplantation
measure: Mortality on the waiting list
time frame: From the date of inclusion until the date of liver transplantation
measure: Infections in the pre-transplantation period
time frame: From the date of inclusion until the date of transplantation
measure: Primary non-function after liver transplantation
time frame: 14 days after the date of liver transplantation
measure: Changes in model for end-stage liver disease score
time frame: From the date of inclusion until the date of transplantation
measure: Changes in Child-Turcotte-Pugh class
time frame: From the date of inclusion until the date of transplantation
measure: Number of hospital admissions due to infections in the pre-transplantation period
time frame: From the date of inclusion until the date of transplantation
measure: Number of hospital admission due to complications of liver cirrhosis in the pre-transplantation period
time frame: From the date of inclusion until the date of transplantation
measure: Serum activity of transaminases on the first 5 postoperative days
time frame: 5 days after the date of liver transplantation
measure: Serum bilirubin concentration in the first 5 postoperative days
time frame: 5 days after the date of liver transplantation
measure: International normalized ratio values during the first 5 postoperative days
time frame: 5 days after the date of liver transplantation
measure: Change in model for end-stage liver disease score in the pre-transplantation period
time frame: 10 weeks
description: To be assessed if the period between inclusion in the study and liver transplantation would not be shorter than 10 weeks
measure: Change in Chil-Turcotte-Pugh class in the pre-transplantation period
time frame: 10 weeks
description: To be assessed if the period between inclusion in the study and liver transplantation would not be shorter than 10 weeks
measure: Changes in faecal microflora
time frame: 10 weeks
description: Differences in the number of colony forming units in 1 g of stool for particular bacterial and fungal species after 10 weeks of probiotic/placebo administration
arm group label: Probiotic
arm group type: Experimental
description: Capsules with 3x10^9 colony forming units (Lactococcus lactis PB 411 - 50%; Lactobacillus casei PB 121 - 25%; Lactobacillus acidophilus PB 111 - 12,5%; Bifidobacterium bifidum PB 211 - 12,5%). 1 capsule a day from inclusion until liver transplantation
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo, 1 capsule a day from inclusion until the date of liver transplantation
intervention type: Dietary Supplement
intervention name: Placebo
description: Placebo, 1 capsule a day from inclusion until the date of liver transplantation
arm group label: Placebo
intervention type: Dietary Supplement
intervention name: Probiotic
description: Capsules with 3x10^9 colony forming units of: Lactococcus lactis PB 411 (50%), Lactobacillus casei PB 121 (25%), Lactobacillus acidophilus PB 111 (12,5%), Bifidobacterium bifidum PB 211 (12,5)
arm group label: Probiotic
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michał Grąt, M.D.
role: Principal Investigator
affiliation: Medical University of Warsaw, Department of General, Transplant and Liver Surgery
last name: Marek Krawczyk, Professor
role: Study Chair
affiliation: Medical University of Warsaw, Department of General, Transplant and Liver Surgery
facility: 
country: Poland
responsible party type: Sponsor
mesh term: Liver Cirrhosis
mesh term: Fibrosis