<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/NCT02190357</url>
  </required_header>
  <id_info>
    <org_study_id>LPDLCC-2</org_study_id>
    <nct_id>NCT02190357</nct_id>
  </id_info>
  <brief_title>Rifaximin Reduces the Complications of Decompensated Cirrhosis: a Randomized Controlled Trial</brief_title>
  <official_title>Rifaximin Reduces the Complications of Decompensated Cirrhosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Changzheng Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Changzheng Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cirrhotic patients are predisposed to intestinal dysmotility, bacterial overgrowth, and&#xD;
      increased intestinal permeability all leading to an increase in bacterial translocation and&#xD;
      increased endotoxemia. Rifaximin is an antibiotic that is virtually non-absorbed after oral&#xD;
      administration and exhibits broad spectrum antimicrobial activity against both aerobic and&#xD;
      anaerobic gram-positive and gram-negative microorganisms within the gastrointestinal tract.&#xD;
      It has been suggested that oral prophylactic antibiotics or bowel decontamination might&#xD;
      improve long-term outcomes in patients with cirrhosis. The aim of this study was to explore&#xD;
      the effect of rifaximin on the complications of advanced cirrhosis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cirrhotic patients are predisposed to intestinal dysmotility, bacterial overgrowth, and&#xD;
      increased intestinal permeability all leading to an increase in bacterial translocation and&#xD;
      increased endotoxemia. Cirrhotics with bacterial translocation and endotoxemia manifest&#xD;
      hemodynamic derangement with lower systemic vascular resistance, higher cardiac output, and&#xD;
      lower mean arterial pressure. Moreover, endotoxins may increase portal pressure by increasing&#xD;
      vascular resistance which may be promoted through the cytokine-stimulated intrahepatic&#xD;
      release of endothelin and cyclo-oxygenase products.&#xD;
&#xD;
      Indeed, bacterial infections are common in cirrhotic patients and have approximately 30%&#xD;
      mortality at one month and a further 30% mortality at 12 months as documented in a systematic&#xD;
      review comprising almost 12 000 patients. It follows that altering gut flora to decrease&#xD;
      endotoxin levels may lead to improved prognosis in cirrhosis. Rifaximin is an antibiotic that&#xD;
      is virtually non-absorbed after oral administration and exhibits broad spectrum antimicrobial&#xD;
      activity against both aerobic and anaerobic gram-positive and gram-negative microorganisms&#xD;
      within the gastrointestinal tract. It has been suggested that oral prophylactic antibiotics&#xD;
      or bowel decontamination might improve long-term outcomes in patients with cirrhosis, not&#xD;
      only by reducing the risk of infections but also by reducing hepatic vein pressure gradient&#xD;
      (HVPG).&#xD;
&#xD;
      The aim of this study was to explore the effect of rifaximin on the complications of advanced&#xD;
      cirrhosis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>August 2014</start_date>
  <completion_date type="Anticipated">August 2019</completion_date>
  <primary_completion_date type="Anticipated">August 2018</primary_completion_date>
  <phase>Phase 4</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>number of death</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>numbers of liver transplantation</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>numbers of hepatic encephalopathy</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Numbers of other complications of cirrhosis</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Cirrhosis</condition>
  <arm_group>
    <arm_group_label>rifaximin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>400 mg bid,orally</description>
  </arm_group>
  <arm_group>
    <arm_group_label>controlled group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>no intervention</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rifaximin</intervention_name>
    <description>Rifaximin is an antibiotic that is virtually non-absorbed after oral administration and exhibits broad spectrum antimicrobial activity against both aerobic and anaerobic gram-positive and gram-negative microorganisms within the gastrointestinal tract.</description>
    <arm_group_label>rifaximin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        1. Eligicility criteria (1) Willing to give written informed consent and comply with the&#xD;
             study restrictions and requirements (2) Age from 18 to 75 years at screening (3)&#xD;
             Clinical diagnosis of decompensated liver cirrhosis&#xD;
&#xD;
          2. Exclusion criteria (1) Episodes of overt hepatic encephalopathy (HE), esophageal&#xD;
             gastric variceal bleeding (EGVB) or spontaneous bacterial peritonitis (SBP) within one&#xD;
             month (2) Hepatitis B Virus (HBV) DNA ≥ 500 copy/ml (3) Standard antiviral treament&#xD;
             duration less than six months for patients receiving antiviral treatment for hepatitis&#xD;
             B or hepatitis C (4) Planned to receive or change the antiviral treament projects at&#xD;
             the screening (5) Unwilling to stop alcohol abuse after inclusion (≥20 g/ d for women&#xD;
             or ≥40 g/d for men) (6) Serum total bilirubin ≥ 170 μmol/L (7) Serum sodium level &lt;&#xD;
             125 mmol/L (8) White blood cell count &lt; 1×109/L (9) Serum creatinine ≥ 1.2 fold of&#xD;
             upper limits of normal (10) Clinically diagnosed or suspected as liver malignancy (11)&#xD;
             Previous use of antibiotics within two weeks before inclusion (12) HIV seropositivity&#xD;
             (13) Poorly controlled hypertension, diabetes mellitus or other severe heart and lung&#xD;
             diseases (14) Known hypersensitivity to rifaximin (15) Pregnancy and lactation woman&#xD;
             (16) Participated in other studies within three months before screening (17) Not&#xD;
             suitble for participating the study judged by investigators&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wei-Fen Xie, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Wei-Fen Xie, MD</last_name>
    <phone>86-21-81885341</phone>
    <email>coss2008@yeah.net</email>
  </overall_contact>
  <location>
    <facility>
      <name>Shanghai changzheng Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200003</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xin Zeng, MD,PhD</last_name>
      <phone>86-21-81885345</phone>
      <email>zengxinmd1978@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Wen-Ping Xu, MD,PhD</last_name>
      <phone>86-21-81885346</phone>
      <email>xwp198527@sina.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <results_reference>
    <citation>Mullen KD, Sanyal AJ, Bass NM, Poordad FF, Sheikh MY, Frederick RT, Bortey E, Forbes WP. Rifaximin is safe and well tolerated for long-term maintenance of remission from overt hepatic encephalopathy. Clin Gastroenterol Hepatol. 2014 Aug;12(8):1390-7.e2. doi: 10.1016/j.cgh.2013.12.021. Epub 2013 Dec 21.</citation>
    <PMID>24365449</PMID>
  </results_reference>
  <results_reference>
    <citation>Xu D, Gao J, Gillilland M 3rd, Wu X, Song I, Kao JY, Owyang C. Rifaximin alters intestinal bacteria and prevents stress-induced gut inflammation and visceral hyperalgesia in rats. Gastroenterology. 2014 Feb;146(2):484-96.e4. doi: 10.1053/j.gastro.2013.10.026. Epub 2013 Oct 22.</citation>
    <PMID>24161699</PMID>
  </results_reference>
  <results_reference>
    <citation>Lutz P, Parcina M, Bekeredjian-Ding I, Hoerauf A, Strassburg CP, Spengler U. Spontaneous bacterial peritonitis by Pasteurella multocida under treatment with rifaximin. Infection. 2014 Feb;42(1):175-7. doi: 10.1007/s15010-013-0449-4. Epub 2013 Mar 25.</citation>
    <PMID>23526308</PMID>
  </results_reference>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>July 10, 2014</study_first_submitted>
  <study_first_submitted_qc>July 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 15, 2014</study_first_posted>
  <last_update_submitted>September 12, 2016</last_update_submitted>
  <last_update_submitted_qc>September 12, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 14, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shanghai Changzheng Hospital</investigator_affiliation>
    <investigator_full_name>Wei-Fen Xie</investigator_full_name>
    <investigator_title>Director</investigator_title>
  </responsible_party>
  <keyword>Cirrhosis</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rifaximin</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/NCT02190357
org study id: LPDLCC-2
nct id: NCT02190357
lead sponsor: 
has dmc: Yes
Cirrhotic patients are predisposed to intestinal dysmotility, bacterial overgrowth, and
      increased intestinal permeability all leading to an increase in bacterial translocation and
      increased endotoxemia. Rifaximin is an antibiotic that is virtually non-absorbed after oral
      administration and exhibits broad spectrum antimicrobial activity against both aerobic and
      anaerobic gram-positive and gram-negative microorganisms within the gastrointestinal tract.
      It has been suggested that oral prophylactic antibiotics or bowel decontamination might
      improve long-term outcomes in patients with cirrhosis. The aim of this study was to explore
      the effect of rifaximin on the complications of advanced cirrhosis.
Cirrhotic patients are predisposed to intestinal dysmotility, bacterial overgrowth, and
      increased intestinal permeability all leading to an increase in bacterial translocation and
      increased endotoxemia. Cirrhotics with bacterial translocation and endotoxemia manifest
      hemodynamic derangement with lower systemic vascular resistance, higher cardiac output, and
      lower mean arterial pressure. Moreover, endotoxins may increase portal pressure by increasing
      vascular resistance which may be promoted through the cytokine-stimulated intrahepatic
      release of endothelin and cyclo-oxygenase products.

      Indeed, bacterial infections are common in cirrhotic patients and have approximately 30%
      mortality at one month and a further 30% mortality at 12 months as documented in a systematic
      review comprising almost 12 000 patients. It follows that altering gut flora to decrease
      endotoxin levels may lead to improved prognosis in cirrhosis. Rifaximin is an antibiotic that
      is virtually non-absorbed after oral administration and exhibits broad spectrum antimicrobial
      activity against both aerobic and anaerobic gram-positive and gram-negative microorganisms
      within the gastrointestinal tract. It has been suggested that oral prophylactic antibiotics
      or bowel decontamination might improve long-term outcomes in patients with cirrhosis, not
      only by reducing the risk of infections but also by reducing hepatic vein pressure gradient
      (HVPG).

      The aim of this study was to explore the effect of rifaximin on the complications of advanced
      cirrhosis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: number of death
time frame: 6 months
measure: numbers of liver transplantation
time frame: 6 months
measure: numbers of hepatic encephalopathy
time frame: 6 months
measure: Numbers of other complications of cirrhosis
time frame: 6 months
arm group label: rifaximin
arm group type: Experimental
description: 400 mg bid,orally
arm group label: controlled group
arm group type: No Intervention
description: no intervention
intervention type: Drug
intervention name: Rifaximin
description: Rifaximin is an antibiotic that is virtually non-absorbed after oral administration and exhibits broad spectrum antimicrobial activity against both aerobic and anaerobic gram-positive and gram-negative microorganisms within the gastrointestinal tract.
arm group label: rifaximin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Wei-Fen Xie, MD
role: Principal Investigator
affiliation: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai
last name: Wei-Fen Xie, MD
phone: 86-21-81885341
email: coss2008@yeah.net
facility: 
status: Recruiting
contact: 
contact backup: 
country: China
citation: Mullen KD, Sanyal AJ, Bass NM, Poordad FF, Sheikh MY, Frederick RT, Bortey E, Forbes WP. Rifaximin is safe and well tolerated for long-term maintenance of remission from overt hepatic encephalopathy. Clin Gastroenterol Hepatol. 2014 Aug;12(8):1390-7.e2. doi: 10.1016/j.cgh.2013.12.021. Epub 2013 Dec 21.
PMID: 24365449
citation: Xu D, Gao J, Gillilland M 3rd, Wu X, Song I, Kao JY, Owyang C. Rifaximin alters intestinal bacteria and prevents stress-induced gut inflammation and visceral hyperalgesia in rats. Gastroenterology. 2014 Feb;146(2):484-96.e4. doi: 10.1053/j.gastro.2013.10.026. Epub 2013 Oct 22.
PMID: 24161699
citation: Lutz P, Parcina M, Bekeredjian-Ding I, Hoerauf A, Strassburg CP, Spengler U. Spontaneous bacterial peritonitis by Pasteurella multocida under treatment with rifaximin. Infection. 2014 Feb;42(1):175-7. doi: 10.1007/s15010-013-0449-4. Epub 2013 Mar 25.
PMID: 23526308
responsible party type: Principal Investigator
investigator affiliation: Shanghai Changzheng Hospital
investigator full name: Wei-Fen Xie
investigator title: Director
mesh term: Liver Cirrhosis
mesh term: Fibrosis
mesh term: Rifaximin