<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/NCT01678326</url>
  </required_header>
  <id_info>
    <org_study_id>2012.061-2-JSha</org_study_id>
    <nct_id>NCT01678326</nct_id>
  </id_info>
  <brief_title>EUS-Guided Rendezvous or Direct Interventions Versus Advanced ERCP Techniques for Biliary Access and Therapy</brief_title>
  <official_title>Endoscopic Ultrasound Guided Rendezvous or Direct Interventions Versus Advanced ERCP Techniques for Biliary Access and Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>California Pacific Medical Center Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Northwestern University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Virginia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of California, Los Angeles</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>California Pacific Medical Center Research Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to prospectively compare the efficacy of endoscopic&#xD;
      ultrasound-guided biliary interventions (EUS-rendezvous or direct EUS-guided therapy) to that&#xD;
      of advanced ERCP cannulation techniques in the setting of difficult cannulation. We&#xD;
      hypothesize that EUS-guided interventions will be more successful and may be associated with&#xD;
      the same complications as using advanced ERCP techniques in cases of difficult bile duct&#xD;
      access.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
      Biliary tract obstruction from stones or strictures are usually treated using endoscopic&#xD;
      retrograde cholangiopancreatography (ERCP) techniques. However, biliary access (cannulation)&#xD;
      during ERCP can be difficult. Overall cannulation success is about 90-95% at expert, centers.&#xD;
      Difficult cannulation is associated with increased complication rates, as prolonged and&#xD;
      repeated attempts can cause injury to the ampulla. When standard biliary cannulation fails&#xD;
      advanced cannulation techniques, such as precut access sphincterotomy, are often indicated.&#xD;
      These advanced techniques, however, increase the complication rate of ERCP, and still fail in&#xD;
      a certain percentage of cases.&#xD;
&#xD;
      Endoscopic ultrasound-guided biliary interventions are relatively newer techniques that have&#xD;
      emerged as a useful option to achieve biliary access or therapy when standard and advanced&#xD;
      ERCP techniques for biliary access have failed. Many centers, including ours, are currently&#xD;
      using EUS-guided interventions to facilitate ERCP access and therapy, when needed. EUS-guided&#xD;
      interventions have emerged as a safe and effective procedure for gaining access to the&#xD;
      biliary tree. A recent retrospective study comparing the safety and efficacy of EUS&#xD;
      rendezvous to precut sphincterotomy (advanced ERCP technique for access), found that&#xD;
      EUS-rendezvous was significantly more successful with no significant difference in the rate&#xD;
      of procedural complications.&#xD;
&#xD;
      Currently, there are no accepted standards for deciding which biliary access technique to use&#xD;
      in cases of difficult biliary cannulation. We hypothesize that EUS-guided biliary&#xD;
      interventions will be more successful and may be associated with the same (or less)&#xD;
      complications than using advanced ERCP techniques in cases of difficult bile duct access.&#xD;
&#xD;
      Procedures:&#xD;
&#xD;
      Patients referred for ERCP for biliary interventions at participating centers will be&#xD;
      approached for consent. Patients who agree to participate will undergo a standard ERCP. The&#xD;
      attending endoscopist will use standard ERCP techniques (i.e. cannulation with a standard&#xD;
      cannula or sphincterotome with or without a wire) to gain biliary access for a minimum of ten&#xD;
      minutes. If biliary access fails, the patient will be randomized to either the EUS-guided&#xD;
      intervention arm or the advanced cannulation techniques arm of the study. The randomization&#xD;
      ratio will be 50-50.&#xD;
&#xD;
      Methods of Data Analysis:&#xD;
&#xD;
      Based on current available data as well as our own experience, we estimated the success for&#xD;
      immediate biliary access for EUS-guided intervention to be 90%, and for advanced ERCP&#xD;
      cannulation techniques to be 75%. To detect this difference with power of 0.8 and a p-value&#xD;
      of &lt;0.05, a sample size of approximately 230 patients will be needed. Assuming that only 10%&#xD;
      of patients that are consented will be randomized (based on the rationale that 90% of&#xD;
      patients will either be successfully cannulated within 10 or will be excluded for other&#xD;
      reasons) we estimate that approximately 2,300 patients will be consented for this study.&#xD;
&#xD;
      As this is the first study of its kind and it is possible that we will achieve statistical&#xD;
      significance at an enrollment number earlier than our anticipated number of 230 participants&#xD;
      two interim analyses are planned for this study. The first interim analysis is scheduled to&#xD;
      occur after the enrollment of 70 patients (35 in each arm) and the second after enrollment of&#xD;
      140 patients (70 in each arm). The block randomization should result in equal numbers of&#xD;
      patients in each arm at these enrollment levels. Adjustment for significance level at each&#xD;
      interim analysis was calculated using the Pocock Boundary method (9). For either of the&#xD;
      interim analyses, the level of significance required for termination of the trial for&#xD;
      efficacy is p = 0.0221. An independent statistician will review the results and make&#xD;
      recommendations regarding study termination based on results of interim analyses.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">December 2019</completion_date>
  <primary_completion_date type="Actual">December 2019</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Biliary access for therapy achieved (wire access across papilla or site of obstruction or wire access to enable successful therapy)</measure>
    <time_frame>24 hours</time_frame>
    <description>Was the endoscopist able to achieve wire access into the biliary system in order to complete the intended therapy? Was intended therapy successful?</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Comparison of adverse events in the two arms.</measure>
    <time_frame>Up to 1 month post procedure.</time_frame>
    <description>Was there a difference in adverse events in the two arms. Adverse events include acute pancreatitis, hematoma, bile leak, etc...</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">226</enrollment>
  <condition>Disorders of Gallbladder</condition>
  <condition>Disorders of Biliary Tract</condition>
  <arm_group>
    <arm_group_label>EUS-Rendezvous or direct intervention</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>EUS rendezvous or direct intervention involves: (1) using endoscopic-ultrasound technology to access the bile duct with a small needle and manipulate a wire across the biliary orifice and into the duodenum to be then retrieved endoscopically for ERCP (rendezvous ERCP), or (2) using endoscopic-ultrasound technology to directly puncture and perform intended biliary therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Advanced ERCP Biliary Access Techniques</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Advanced ERCP techniques involve the following: precut access sphincterotomy and needle-knife fistulotomy. These are accepted techniques for biliary access in cases of difficult cannulation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>EUS-Rendezvous or direct intervention</intervention_name>
    <arm_group_label>EUS-Rendezvous or direct intervention</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Advanced ERCP Biliary Access Techniques</intervention_name>
    <arm_group_label>Advanced ERCP Biliary Access Techniques</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients able to give informed consent&#xD;
&#xD;
          -  Patients referred to participating centers for ERCP with the intent to cannulate the&#xD;
             bile duct for therapy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with a bleeding diathesis (INR &gt;1.4, platelets &lt;80, current use of&#xD;
             anticoagulant medications)&#xD;
&#xD;
          -  Patients whose bile ducts are cannulated using standard methods&#xD;
&#xD;
          -  Patients with prior biliary sphincterotomy or endoscopic papilla dilation&#xD;
&#xD;
          -  Patients with previous surgical biliary-intestinal operations&#xD;
&#xD;
          -  Patients with pancreas divisum&#xD;
&#xD;
          -  Patients with indwelling pancreatic or biliary stent placement&#xD;
&#xD;
          -  Patients who are pregnant or breast-feeding&#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>Christopher Hamerski, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>California Pacific Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>California Pacific Medical Center</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Carr-Locke DL. Overview of the role of ERCP in the management of diseases of the biliary tract and the pancreas. Gastrointest Endosc. 2002 Dec;56(6 Suppl):S157-60. doi: 10.1067/mge.2002.129023. No abstract available.</citation>
    <PMID>12447259</PMID>
  </reference>
  <reference>
    <citation>Shah JN, Marson F, Weilert F, Bhat YM, Nguyen-Tang T, Shaw RE, Binmoeller KF. Single-operator, single-session EUS-guided anterograde cholangiopancreatography in failed ERCP or inaccessible papilla. Gastrointest Endosc. 2012 Jan;75(1):56-64. doi: 10.1016/j.gie.2011.08.032. Epub 2011 Oct 21.</citation>
    <PMID>22018554</PMID>
  </reference>
  <reference>
    <citation>Johnson GK, Geenen JE, Johanson JF, Sherman S, Hogan WJ, Cass O. Evaluation of post-ERCP pancreatitis: potential causes noted during controlled study of differing contrast media. Midwest Pancreaticobiliary Study Group. Gastrointest Endosc. 1997 Sep;46(3):217-22. doi: 10.1016/s0016-5107(97)70089-0.</citation>
    <PMID>9378207</PMID>
  </reference>
  <reference>
    <citation>Freeman ML, Nelson DB, Sherman S, Haber GB, Herman ME, Dorsher PJ, Moore JP, Fennerty MB, Ryan ME, Shaw MJ, Lande JD, Pheley AM. Complications of endoscopic biliary sphincterotomy. N Engl J Med. 1996 Sep 26;335(13):909-18. doi: 10.1056/NEJM199609263351301.</citation>
    <PMID>8782497</PMID>
  </reference>
  <reference>
    <citation>Angsuwatcharakon P, Rerknimitr R, Ridtitid W, Ponauthai Y, Kullavanijaya P. Success rate and cannulation time between precut sphincterotomy and double-guidewire technique in truly difficult biliary cannulation. J Gastroenterol Hepatol. 2012 Feb;27(2):356-61. doi: 10.1111/j.1440-1746.2011.06927.x.</citation>
    <PMID>21916994</PMID>
  </reference>
  <reference>
    <citation>Masci E, Toti G, Mariani A, Curioni S, Lomazzi A, Dinelli M, Minoli G, Crosta C, Comin U, Fertitta A, Prada A, Passoni GR, Testoni PA. Complications of diagnostic and therapeutic ERCP: a prospective multicenter study. Am J Gastroenterol. 2001 Feb;96(2):417-23. doi: 10.1111/j.1572-0241.2001.03594.x.</citation>
    <PMID>11232684</PMID>
  </reference>
  <reference>
    <citation>Wang P, Li ZS, Liu F, Ren X, Lu NH, Fan ZN, Huang Q, Zhang X, He LP, Sun WS, Zhao Q, Shi RH, Tian ZB, Li YQ, Li W, Zhi FC. Risk factors for ERCP-related complications: a prospective multicenter study. Am J Gastroenterol. 2009 Jan;104(1):31-40. doi: 10.1038/ajg.2008.5.</citation>
    <PMID>19098846</PMID>
  </reference>
  <reference>
    <citation>Dhir V, Bhandari S, Bapat M, Maydeo A. Comparison of EUS-guided rendezvous and precut papillotomy techniques for biliary access (with videos). Gastrointest Endosc. 2012 Feb;75(2):354-9. doi: 10.1016/j.gie.2011.07.075.</citation>
    <PMID>22248603</PMID>
  </reference>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>August 29, 2012</study_first_submitted>
  <study_first_submitted_qc>September 4, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 5, 2012</study_first_posted>
  <last_update_submitted>February 6, 2020</last_update_submitted>
  <last_update_submitted_qc>February 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 7, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>California Pacific Medical Center Research Institute</investigator_affiliation>
    <investigator_full_name>Christopher Hemerski</investigator_full_name>
    <investigator_title>Director of Luminal Oncology</investigator_title>
  </responsible_party>
  <keyword>Diseases Classified Elsewhere</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gallbladder Diseases</mesh_term>
    <mesh_term>Biliary Tract Diseases</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/NCT01678326
org study id: 2012.061-2-JSha
nct id: NCT01678326
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
The purpose of this study is to prospectively compare the efficacy of endoscopic
      ultrasound-guided biliary interventions (EUS-rendezvous or direct EUS-guided therapy) to that
      of advanced ERCP cannulation techniques in the setting of difficult cannulation. We
      hypothesize that EUS-guided interventions will be more successful and may be associated with
      the same complications as using advanced ERCP techniques in cases of difficult bile duct
      access.
Background:

      Biliary tract obstruction from stones or strictures are usually treated using endoscopic
      retrograde cholangiopancreatography (ERCP) techniques. However, biliary access (cannulation)
      during ERCP can be difficult. Overall cannulation success is about 90-95% at expert, centers.
      Difficult cannulation is associated with increased complication rates, as prolonged and
      repeated attempts can cause injury to the ampulla. When standard biliary cannulation fails
      advanced cannulation techniques, such as precut access sphincterotomy, are often indicated.
      These advanced techniques, however, increase the complication rate of ERCP, and still fail in
      a certain percentage of cases.

      Endoscopic ultrasound-guided biliary interventions are relatively newer techniques that have
      emerged as a useful option to achieve biliary access or therapy when standard and advanced
      ERCP techniques for biliary access have failed. Many centers, including ours, are currently
      using EUS-guided interventions to facilitate ERCP access and therapy, when needed. EUS-guided
      interventions have emerged as a safe and effective procedure for gaining access to the
      biliary tree. A recent retrospective study comparing the safety and efficacy of EUS
      rendezvous to precut sphincterotomy (advanced ERCP technique for access), found that
      EUS-rendezvous was significantly more successful with no significant difference in the rate
      of procedural complications.

      Currently, there are no accepted standards for deciding which biliary access technique to use
      in cases of difficult biliary cannulation. We hypothesize that EUS-guided biliary
      interventions will be more successful and may be associated with the same (or less)
      complications than using advanced ERCP techniques in cases of difficult bile duct access.

      Procedures:

      Patients referred for ERCP for biliary interventions at participating centers will be
      approached for consent. Patients who agree to participate will undergo a standard ERCP. The
      attending endoscopist will use standard ERCP techniques (i.e. cannulation with a standard
      cannula or sphincterotome with or without a wire) to gain biliary access for a minimum of ten
      minutes. If biliary access fails, the patient will be randomized to either the EUS-guided
      intervention arm or the advanced cannulation techniques arm of the study. The randomization
      ratio will be 50-50.

      Methods of Data Analysis:

      Based on current available data as well as our own experience, we estimated the success for
      immediate biliary access for EUS-guided intervention to be 90%, and for advanced ERCP
      cannulation techniques to be 75%. To detect this difference with power of 0.8 and a p-value
      of <0.05, a sample size of approximately 230 patients will be needed. Assuming that only 10%
      of patients that are consented will be randomized (based on the rationale that 90% of
      patients will either be successfully cannulated within 10 or will be excluded for other
      reasons) we estimate that approximately 2,300 patients will be consented for this study.

      As this is the first study of its kind and it is possible that we will achieve statistical
      significance at an enrollment number earlier than our anticipated number of 230 participants
      two interim analyses are planned for this study. The first interim analysis is scheduled to
      occur after the enrollment of 70 patients (35 in each arm) and the second after enrollment of
      140 patients (70 in each arm). The block randomization should result in equal numbers of
      patients in each arm at these enrollment levels. Adjustment for significance level at each
      interim analysis was calculated using the Pocock Boundary method (9). For either of the
      interim analyses, the level of significance required for termination of the trial for
      efficacy is p = 0.0221. An independent statistician will review the results and make
      recommendations regarding study termination based on results of interim analyses.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Biliary access for therapy achieved (wire access across papilla or site of obstruction or wire access to enable successful therapy)
time frame: 24 hours
description: Was the endoscopist able to achieve wire access into the biliary system in order to complete the intended therapy? Was intended therapy successful?
measure: Comparison of adverse events in the two arms.
time frame: Up to 1 month post procedure.
description: Was there a difference in adverse events in the two arms. Adverse events include acute pancreatitis, hematoma, bile leak, etc...
arm group label: EUS-Rendezvous or direct intervention
arm group type: Active Comparator
description: EUS rendezvous or direct intervention involves: (1) using endoscopic-ultrasound technology to access the bile duct with a small needle and manipulate a wire across the biliary orifice and into the duodenum to be then retrieved endoscopically for ERCP (rendezvous ERCP), or (2) using endoscopic-ultrasound technology to directly puncture and perform intended biliary therapy
arm group label: Advanced ERCP Biliary Access Techniques
arm group type: Active Comparator
description: Advanced ERCP techniques involve the following: precut access sphincterotomy and needle-knife fistulotomy. These are accepted techniques for biliary access in cases of difficult cannulation.
intervention type: Procedure
intervention name: EUS-Rendezvous or direct intervention
arm group label: EUS-Rendezvous or direct intervention
intervention type: Procedure
intervention name: Advanced ERCP Biliary Access Techniques
arm group label: Advanced ERCP Biliary Access Techniques
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Christopher Hamerski, M.D.
role: Principal Investigator
affiliation: California Pacific Medical Center
facility: 
country: United States
citation: Carr-Locke DL. Overview of the role of ERCP in the management of diseases of the biliary tract and the pancreas. Gastrointest Endosc. 2002 Dec;56(6 Suppl):S157-60. doi: 10.1067/mge.2002.129023. No abstract available.
PMID: 12447259
citation: Shah JN, Marson F, Weilert F, Bhat YM, Nguyen-Tang T, Shaw RE, Binmoeller KF. Single-operator, single-session EUS-guided anterograde cholangiopancreatography in failed ERCP or inaccessible papilla. Gastrointest Endosc. 2012 Jan;75(1):56-64. doi: 10.1016/j.gie.2011.08.032. Epub 2011 Oct 21.
PMID: 22018554
citation: Johnson GK, Geenen JE, Johanson JF, Sherman S, Hogan WJ, Cass O. Evaluation of post-ERCP pancreatitis: potential causes noted during controlled study of differing contrast media. Midwest Pancreaticobiliary Study Group. Gastrointest Endosc. 1997 Sep;46(3):217-22. doi: 10.1016/s0016-5107(97)70089-0.
PMID: 9378207
citation: Freeman ML, Nelson DB, Sherman S, Haber GB, Herman ME, Dorsher PJ, Moore JP, Fennerty MB, Ryan ME, Shaw MJ, Lande JD, Pheley AM. Complications of endoscopic biliary sphincterotomy. N Engl J Med. 1996 Sep 26;335(13):909-18. doi: 10.1056/NEJM199609263351301.
PMID: 8782497
citation: Angsuwatcharakon P, Rerknimitr R, Ridtitid W, Ponauthai Y, Kullavanijaya P. Success rate and cannulation time between precut sphincterotomy and double-guidewire technique in truly difficult biliary cannulation. J Gastroenterol Hepatol. 2012 Feb;27(2):356-61. doi: 10.1111/j.1440-1746.2011.06927.x.
PMID: 21916994
citation: Masci E, Toti G, Mariani A, Curioni S, Lomazzi A, Dinelli M, Minoli G, Crosta C, Comin U, Fertitta A, Prada A, Passoni GR, Testoni PA. Complications of diagnostic and therapeutic ERCP: a prospective multicenter study. Am J Gastroenterol. 2001 Feb;96(2):417-23. doi: 10.1111/j.1572-0241.2001.03594.x.
PMID: 11232684
citation: Wang P, Li ZS, Liu F, Ren X, Lu NH, Fan ZN, Huang Q, Zhang X, He LP, Sun WS, Zhao Q, Shi RH, Tian ZB, Li YQ, Li W, Zhi FC. Risk factors for ERCP-related complications: a prospective multicenter study. Am J Gastroenterol. 2009 Jan;104(1):31-40. doi: 10.1038/ajg.2008.5.
PMID: 19098846
citation: Dhir V, Bhandari S, Bapat M, Maydeo A. Comparison of EUS-guided rendezvous and precut papillotomy techniques for biliary access (with videos). Gastrointest Endosc. 2012 Feb;75(2):354-9. doi: 10.1016/j.gie.2011.07.075.
PMID: 22248603
responsible party type: Principal Investigator
investigator affiliation: California Pacific Medical Center Research Institute
investigator full name: Christopher Hemerski
investigator title: Director of Luminal Oncology
mesh term: Gallbladder Diseases
mesh term: Biliary Tract Diseases