<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/NCT01688375</url>
  </required_header>
  <id_info>
    <org_study_id>E25071969F</org_study_id>
    <secondary_id>EN1969FE</secondary_id>
    <nct_id>NCT01688375</nct_id>
  </id_info>
  <brief_title>The Effect of Ursodeoxycholic Acid in Liver Functional Restoration of Patients With Obstructive Jaundice</brief_title>
  <official_title>The Effect of Ursodeoxycholic Acid in Liver Functional Restoration of Patients With Obstructive Jaundice After Endoscopic or Surgical Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Clinical Centre of Kosova</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Zagreb</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Clinical Centre of Kosova</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      ABSTRACT:&#xD;
&#xD;
      In patients with obstructive jaundice, multi-organ dysfunction may develop. The aim of this&#xD;
      study is to evaluate the effect of ursodeoxycholic acid on liver functional restoration on&#xD;
      patients with obstructive jaundice after surgical or endoscopic treatment.&#xD;
&#xD;
      Patients with obstructive jaundice will be divided into two groups: (A) test group in which&#xD;
      will be administered ursodeoxycholic acid twenty-four hours after endoscopic or surgical&#xD;
      procedure and will last fourteen days, and (B) control group.&#xD;
&#xD;
      Serum-testing will include determination of bilirubin, alanine transaminase, aspartate&#xD;
      transaminase, gama-glutamyl transpeptidase, alkaline phosphatase, albumin, and cholesterol&#xD;
      levels. These parameters will be determined one day prior endoscopic or surgical procedure,&#xD;
      and on the third, fifth, seventh, tenth, twelfth and fourteenth days after endoscopic or&#xD;
      surgical intervention.&#xD;
&#xD;
      Our hypothesis is that patients with obstructive jaundice under treatment with&#xD;
      ursodeoxycholic acid will have better outcome than patients in control group.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study objectives:&#xD;
&#xD;
      This trial will be a prospective, an open, randomized and controlled study. The objective&#xD;
      will be to evaluate the effect of ursodeoxycholic acid (UDCA) in the functional restoration&#xD;
      of the liver in patients with obstructive jaundice in the early post-endoscopic or&#xD;
      post-surgical phase.&#xD;
&#xD;
      Study design:&#xD;
&#xD;
      After diagnosis, patients with obstructive jaundice will be divided into two groups: (A) the&#xD;
      test group in which will be administered UDCA in the early phase after endoscopic or surgical&#xD;
      treatment, and (B) control group, in which no treatment will be applied with UDCA.&#xD;
&#xD;
      Diagnostic methods will be biochemical findings, ultrasound examination, endoscopic&#xD;
      retrograde cholangio pancreatography (ERCP), CT-scan and magnetic resonance cholangio&#xD;
      pancreatography (MRCP).&#xD;
&#xD;
      Serum-testing in patients with obstructive jaundice will include determination of bilirubin&#xD;
      (total and direct fractions), alanine transaminase (ALT), aspartate transaminase (AST),&#xD;
      gama-glutamyl transpeptidase (GGT), alkaline phosphatase, albumin, and cholesterol levels.&#xD;
      These parameters will be determined one day prior endoscopic or surgical intervention, and on&#xD;
      the third, fifth, seventh, tenth, twelfth and fourteenth days after endoscopic or surgical&#xD;
      intervention.&#xD;
&#xD;
      Endoscope and surgical procedures that will end with the external derivation of bile will be&#xD;
      named as the external bile drainage, and indeed, while endoscope and surgical procedures that&#xD;
      will make the internal derivation of bile shall be named as the internal bile drainage.&#xD;
&#xD;
      UDCA administration:&#xD;
&#xD;
      UDCA administration will begin twenty-four hours after endoscopic or surgical procedure and&#xD;
      will last fourteen days. UDCA dose will be administered at 750 mg/day, divided into three&#xD;
      doses.&#xD;
&#xD;
      Power of the study:&#xD;
&#xD;
      A clinically relevant improvement of liver functional tests is defined as an improvement of&#xD;
      80% of liver functional tests in test group, and an improvement only 40% in control group. In&#xD;
      our study, to have an 80% chance of detecting a 50% difference between two groups on&#xD;
      improvement of liver functional tests at an alpha level of 0.05, the power calculation&#xD;
      indicates that each of the two groups should have at least 27 patients.&#xD;
&#xD;
      Data sources and search strategy:&#xD;
&#xD;
      An electronic search was performed on PubMed (from 1 January 1985 to 1 February 2012). A&#xD;
      combination of keywords and MeSH terms where: 'ursodeoxycholic acid' AND 'obstructive&#xD;
      jaundice', 'obstructive jaundice' AND 'liver function tests', 'obstructive jaundice' AND&#xD;
      'acute renal failure'. I have used , also, limits: Type of article ( selection was- clinical&#xD;
      trial, meta-analyses), Species( selection was- human, animals), Text options ( selection was-&#xD;
      links to free full text, abstract), Languages( English), Sex ( male, female), Age ( all adult&#xD;
      19+ years), Field ( all fields).&#xD;
&#xD;
      Randomization:&#xD;
&#xD;
      Patients have to sign an informed consent for the involving in the trial a day before&#xD;
      endoscopic or surgical procedure. Randomisation will be performed at the time of transfer to&#xD;
      the endoscope or operating room.&#xD;
&#xD;
      Ethics:&#xD;
&#xD;
      This study will be realized in the Surgery Clinic (Department of Abdominal Surgery) at&#xD;
      University Clinical Centre of Kosovo in Pristina. It will be conducted in accordance with the&#xD;
      principles of the Declaration of Helsinki. This study will begin after approval of the study&#xD;
      protocol by Medical Ethics Committee of the University Clinical Centre of Kosovo( Faculty of&#xD;
      Medicine).&#xD;
&#xD;
      Data collection and statistical analyses:&#xD;
&#xD;
      Data including serum-test results will be collected in a computer secured study platform.&#xD;
      These data will be collected continuously, for each patient, starting one day before&#xD;
      endoscopic or surgical procedure until the last data fourteen days after intervention.&#xD;
&#xD;
      X2-analysis or Fisher exact test will perform to test the differences in proportions of&#xD;
      qualitative variables between groups. Mann Whitney U test and Kruskal Wallis test will use&#xD;
      for testing the difference between quantitative variables when distribution is not normal and&#xD;
      Student t-test or ANOVA test when distribution is normal. The level P&lt;0.05 will consider as&#xD;
      the cut-off value for significance.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>December 2012</start_date>
  <completion_date type="Anticipated">December 2013</completion_date>
  <primary_completion_date type="Anticipated">July 2013</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Liver functional restoration</measure>
    <time_frame>Within 14 days after treatment with ursodeoxycholic acid</time_frame>
    <description>Serum-testing in patients with obstructive jaundice will include determination of bilirubin (total and direct fractions), alanine transaminase (ALT), aspartate transaminase (AST), gama-glutamyl transpeptidase (GGT), alkaline phosphatase, albumin, and cholesterol levels.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To assess that in which functional parameters of the liver, treatment with UDCA will have greater impact</measure>
    <time_frame>within 14 days after treatment with ursodeoxycholic acid</time_frame>
    <description>determination of bilirubin (total and direct fractions), alanine transaminase (ALT), aspartate transaminase (AST), gama-glutamyl transpeptidase (GGT), alkaline phosphatase, albumin, and cholesterol levels. These parameters will be determined one day prior endoscopic or surgical intervention, and on the third, fifth, seventh, tenth, twelfth and fourteenth days after endoscopic or surgical intervention.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">54</enrollment>
  <condition>Obstructive Jaundice</condition>
  <arm_group>
    <arm_group_label>Ursodeoxycholic acid</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ursodeoxycholic acid administration UDCA administration will begin twenty-four hours after endoscopic or surgical procedure and will last fourteen days. UDCA dose will be administered at 750 mg/day, divided into three doses.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ursodeoxycholic Acid</intervention_name>
    <description>UDCA administration will begin twenty-four hours after endoscopic or surgical procedure and will last fourteen days. UDCA dose will be administered at 750 mg/day, divided into three doses.</description>
    <arm_group_label>Ursodeoxycholic acid</arm_group_label>
    <other_name>Ursofalk, UDCA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Patients with obstructive jaundice&#xD;
&#xD;
          -  Serum bilirubin level higher than 50 micromole/l&#xD;
&#xD;
          -  19+ years of age&#xD;
&#xD;
          -  written informed consent&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Cholangitis&#xD;
&#xD;
          -  Acute pancreatitis&#xD;
&#xD;
          -  pregnant women&#xD;
&#xD;
          -  women during the breastfeeding&#xD;
&#xD;
          -  suspected or proven primary liver diseases&#xD;
&#xD;
          -  My family members&#xD;
&#xD;
          -  Patients who are unable to understand our study purpose&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Enver H Fekaj, PhD student</last_name>
    <role>Principal Investigator</role>
    <affiliation>University clinical centre of Kosovo, Department of surgery</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Enver H Fekaj, PhD student</last_name>
    <phone>+37744279296</phone>
    <email>enverfekaj@hotmail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>University clinical centre of Kosovo, Department of general surgery</name>
      <address>
        <city>Pristina</city>
        <state>Kosovo</state>
        <zip>10000</zip>
        <country>Serbia</country>
      </address>
    </facility>
    <contact>
      <last_name>Enver H Fekaj, PhD student</last_name>
      <phone>37744279296</phone>
      <email>enverfekaj@hotmail.com</email>
    </contact>
    <investigator>
      <last_name>Enver H Fekaj, PhD student</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University clinical centre of Kosovo</name>
      <address>
        <city>Pristina</city>
        <state>Kosovo</state>
        <zip>10000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University clinical centre of Kosovo</name>
      <address>
        <city>Pristina</city>
        <state>Kosovo</state>
        <zip>10000</zip>
        <country>Serbia</country>
      </address>
    </facility>
    <contact>
      <last_name>Enver H Fekaj, PhD student</last_name>
      <phone>37744279296</phone>
      <email>enverfekaj@hotmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Serbia</country>
  </location_countries>
  <reference>
    <citation>1. Roche SP, Kobos R. Jaundice in the adult patient. Am Fam Physician. 2004; 69(2):299-304. 2. Rerknimitr R, Kullavanijaya P. Operable malignant jaundice: To stent or not to stent before the operation? World J Gastrointest Endosc. 2010; 2(1):10-4. 3.Yi-Jun Y, Jing-Sen SH, Shu-Min X, De-Ting ZH, Bing-Sheng C. Effects of different drainage procedures on levels of serum endotoxin and tumor necrosis factor in patients with malignant obstructive jaundice. HBPD Int. 2003;2:426-30. 4.Scott-Conner CE, Grogan JB. The pathophysiology of biliary obstruction and its effect on phagocytic and immune function. J Surg Res. 1994;57(2):316-36. 5.Assimakopoulos SF, Scopa ChD, Vaginos CE. Pathophysiology of increased intestinal permeability in obstructive jaundice. World J Gastroenterol. 2007;13(48):6458-64.</citation>
  </reference>
  <verification_date>September 2012</verification_date>
  <study_first_submitted>September 11, 2012</study_first_submitted>
  <study_first_submitted_qc>September 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 19, 2012</study_first_posted>
  <last_update_submitted>October 1, 2012</last_update_submitted>
  <last_update_submitted_qc>October 1, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 2, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Clinical Centre of Kosova</investigator_affiliation>
    <investigator_full_name>Enver Fekaj</investigator_full_name>
    <investigator_title>General surgeon, PhD student</investigator_title>
  </responsible_party>
  <keyword>obstructive jaundice</keyword>
  <keyword>ursodeoxycholic acid</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Jaundice</mesh_term>
    <mesh_term>Jaundice, Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ursodeoxycholic Acid</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/NCT01688375
org study id: E25071969F
secondary id: EN1969FE
nct id: NCT01688375
lead sponsor: 
collaborator: 
has dmc: No
ABSTRACT:

      In patients with obstructive jaundice, multi-organ dysfunction may develop. The aim of this
      study is to evaluate the effect of ursodeoxycholic acid on liver functional restoration on
      patients with obstructive jaundice after surgical or endoscopic treatment.

      Patients with obstructive jaundice will be divided into two groups: (A) test group in which
      will be administered ursodeoxycholic acid twenty-four hours after endoscopic or surgical
      procedure and will last fourteen days, and (B) control group.

      Serum-testing will include determination of bilirubin, alanine transaminase, aspartate
      transaminase, gama-glutamyl transpeptidase, alkaline phosphatase, albumin, and cholesterol
      levels. These parameters will be determined one day prior endoscopic or surgical procedure,
      and on the third, fifth, seventh, tenth, twelfth and fourteenth days after endoscopic or
      surgical intervention.

      Our hypothesis is that patients with obstructive jaundice under treatment with
      ursodeoxycholic acid will have better outcome than patients in control group.
Study objectives:

      This trial will be a prospective, an open, randomized and controlled study. The objective
      will be to evaluate the effect of ursodeoxycholic acid (UDCA) in the functional restoration
      of the liver in patients with obstructive jaundice in the early post-endoscopic or
      post-surgical phase.

      Study design:

      After diagnosis, patients with obstructive jaundice will be divided into two groups: (A) the
      test group in which will be administered UDCA in the early phase after endoscopic or surgical
      treatment, and (B) control group, in which no treatment will be applied with UDCA.

      Diagnostic methods will be biochemical findings, ultrasound examination, endoscopic
      retrograde cholangio pancreatography (ERCP), CT-scan and magnetic resonance cholangio
      pancreatography (MRCP).

      Serum-testing in patients with obstructive jaundice will include determination of bilirubin
      (total and direct fractions), alanine transaminase (ALT), aspartate transaminase (AST),
      gama-glutamyl transpeptidase (GGT), alkaline phosphatase, albumin, and cholesterol levels.
      These parameters will be determined one day prior endoscopic or surgical intervention, and on
      the third, fifth, seventh, tenth, twelfth and fourteenth days after endoscopic or surgical
      intervention.

      Endoscope and surgical procedures that will end with the external derivation of bile will be
      named as the external bile drainage, and indeed, while endoscope and surgical procedures that
      will make the internal derivation of bile shall be named as the internal bile drainage.

      UDCA administration:

      UDCA administration will begin twenty-four hours after endoscopic or surgical procedure and
      will last fourteen days. UDCA dose will be administered at 750 mg/day, divided into three
      doses.

      Power of the study:

      A clinically relevant improvement of liver functional tests is defined as an improvement of
      80% of liver functional tests in test group, and an improvement only 40% in control group. In
      our study, to have an 80% chance of detecting a 50% difference between two groups on
      improvement of liver functional tests at an alpha level of 0.05, the power calculation
      indicates that each of the two groups should have at least 27 patients.

      Data sources and search strategy:

      An electronic search was performed on PubMed (from 1 January 1985 to 1 February 2012). A
      combination of keywords and MeSH terms where: 'ursodeoxycholic acid' AND 'obstructive
      jaundice', 'obstructive jaundice' AND 'liver function tests', 'obstructive jaundice' AND
      'acute renal failure'. I have used , also, limits: Type of article ( selection was- clinical
      trial, meta-analyses), Species( selection was- human, animals), Text options ( selection was-
      links to free full text, abstract), Languages( English), Sex ( male, female), Age ( all adult
      19+ years), Field ( all fields).

      Randomization:

      Patients have to sign an informed consent for the involving in the trial a day before
      endoscopic or surgical procedure. Randomisation will be performed at the time of transfer to
      the endoscope or operating room.

      Ethics:

      This study will be realized in the Surgery Clinic (Department of Abdominal Surgery) at
      University Clinical Centre of Kosovo in Pristina. It will be conducted in accordance with the
      principles of the Declaration of Helsinki. This study will begin after approval of the study
      protocol by Medical Ethics Committee of the University Clinical Centre of Kosovo( Faculty of
      Medicine).

      Data collection and statistical analyses:

      Data including serum-test results will be collected in a computer secured study platform.
      These data will be collected continuously, for each patient, starting one day before
      endoscopic or surgical procedure until the last data fourteen days after intervention.

      X2-analysis or Fisher exact test will perform to test the differences in proportions of
      qualitative variables between groups. Mann Whitney U test and Kruskal Wallis test will use
      for testing the difference between quantitative variables when distribution is not normal and
      Student t-test or ANOVA test when distribution is normal. The level P<0.05 will consider as
      the cut-off value for significance.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Supportive Care
masking: None (Open Label)
measure: Liver functional restoration
time frame: Within 14 days after treatment with ursodeoxycholic acid
description: Serum-testing in patients with obstructive jaundice will include determination of bilirubin (total and direct fractions), alanine transaminase (ALT), aspartate transaminase (AST), gama-glutamyl transpeptidase (GGT), alkaline phosphatase, albumin, and cholesterol levels.
measure: To assess that in which functional parameters of the liver, treatment with UDCA will have greater impact
time frame: within 14 days after treatment with ursodeoxycholic acid
description: determination of bilirubin (total and direct fractions), alanine transaminase (ALT), aspartate transaminase (AST), gama-glutamyl transpeptidase (GGT), alkaline phosphatase, albumin, and cholesterol levels. These parameters will be determined one day prior endoscopic or surgical intervention, and on the third, fifth, seventh, tenth, twelfth and fourteenth days after endoscopic or surgical intervention.
arm group label: Ursodeoxycholic acid
arm group type: Experimental
description: Ursodeoxycholic acid administration UDCA administration will begin twenty-four hours after endoscopic or surgical procedure and will last fourteen days. UDCA dose will be administered at 750 mg/day, divided into three doses.
intervention type: Drug
intervention name: Ursodeoxycholic Acid
description: UDCA administration will begin twenty-four hours after endoscopic or surgical procedure and will last fourteen days. UDCA dose will be administered at 750 mg/day, divided into three doses.
arm group label: Ursodeoxycholic acid
other name: Ursofalk, UDCA
criteria: 
gender: All
minimum age: 19 Years
maximum age: 80 Years
healthy volunteers: No
last name: Enver H Fekaj, PhD student
role: Principal Investigator
affiliation: University clinical centre of Kosovo, Department of surgery
last name: Enver H Fekaj, PhD student
phone: +37744279296
email: enverfekaj@hotmail.com
facility: 
contact: 
investigator: 
facility: 
facility: 
contact: 
country: Serbia
citation: 1. Roche SP, Kobos R. Jaundice in the adult patient. Am Fam Physician. 2004; 69(2):299-304. 2. Rerknimitr R, Kullavanijaya P. Operable malignant jaundice: To stent or not to stent before the operation? World J Gastrointest Endosc. 2010; 2(1):10-4. 3.Yi-Jun Y, Jing-Sen SH, Shu-Min X, De-Ting ZH, Bing-Sheng C. Effects of different drainage procedures on levels of serum endotoxin and tumor necrosis factor in patients with malignant obstructive jaundice. HBPD Int. 2003;2:426-30. 4.Scott-Conner CE, Grogan JB. The pathophysiology of biliary obstruction and its effect on phagocytic and immune function. J Surg Res. 1994;57(2):316-36. 5.Assimakopoulos SF, Scopa ChD, Vaginos CE. Pathophysiology of increased intestinal permeability in obstructive jaundice. World J Gastroenterol. 2007;13(48):6458-64.
responsible party type: Principal Investigator
investigator affiliation: University Clinical Centre of Kosova
investigator full name: Enver Fekaj
investigator title: General surgeon, PhD student
mesh term: Jaundice
mesh term: Jaundice, Obstructive
mesh term: Ursodeoxycholic Acid