<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/NCT03812432</url>
  </required_header>
  <id_info>
    <org_study_id>XMOL16012019</org_study_id>
    <nct_id>NCT03812432</nct_id>
  </id_info>
  <brief_title>Cholecystocholangiography by Direct Intragallbladder Injection of ICG</brief_title>
  <official_title>Near-infrared Fluorescence Cholecystocholangiography by Direct Intragallbladder Indocyanine Green Injection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Son Espases</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital Son Espases</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this clinical trial is to visualize the bile ducts by injecting a contrast&#xD;
      that is only visible with infrared light. For this, a quantity of bile will be extracted from&#xD;
      the gallbladder by puncture and the same amount of contrast will be introduced.&#xD;
&#xD;
      During the intervention teh tissue wil be exposure to infrared light to visualize the bile&#xD;
      ducts. This technique aims to increase safety in surgery to avoid damaging bile or vascular&#xD;
      structures during gallbladder interventions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Laparoscopic cholecystectomy is one of the most commonly performed procedures in adult&#xD;
      surgery. A rare but serious complication of laparoscopic cholecystectomy is bile duct injury,&#xD;
      with a reported incidence of 0.3-1.5 %. Bile duct injury is often caused by misinterpretation&#xD;
      of the anatomical structures rather than by insufficient technical skills. Generally, bile&#xD;
      duct injury leads to bile leakage, causing abdominal sepsis. It can also lead to obstruction,&#xD;
      with obstructive jaundice, eventually potentially leading to a need for liver transplantation&#xD;
      in the worst case. Late recognition is common in bile duct injuries, resulting in significant&#xD;
      morbidity and mortality, a lower quality of life and extra costs. A recent expert consensus&#xD;
      report identified establishment of the critical view of safety as the single most important&#xD;
      factor for overall safety during laparoscopic cholecystectomy. However, evidence suggests&#xD;
      that surgeons may actually achieve this view far less often than they believe.&#xD;
&#xD;
      Numerous intraoperative visualization techniques and technologies have been developed to&#xD;
      enhance the safety of laparoscopic cholecystectomy. There are mainly two intraoperative&#xD;
      imaging techniques to consider: first, the historical X-ray-based intraoperative&#xD;
      cholangiography, and secondly the emerging fluorescence-based intraoperative near-infrared&#xD;
      cholangiography. Large retrospective and prospective studies have looked at the benefit of&#xD;
      routine intraoperative radiographic cholangiography for detection of common bile duct stones&#xD;
      and to identify or prevent bile duct injury. Whether this procedure should be performed&#xD;
      routinely is still an active subject of debate as systematic reviews are inconclusive;&#xD;
      however, several of the larger retrospective studies observed a decrease in frequency and&#xD;
      severity of bile duct injury when intraoperative cholangiography is performed. Limiting&#xD;
      factors for performing radiographic laparoscopic cholangiography include: it requires&#xD;
      specific expertise in the technique and its interpretation; it involves the use of ionizing&#xD;
      radiation; it is time-consuming; and it creates a risk for bile leakage and duct injury&#xD;
      itself, since puncturing and cannulation of the cystic duct is required. These limitations&#xD;
      justify the quest for alternative, less complicated techniques to visualize biliary anatomy&#xD;
      during cholecystectomy. Fluorescence-based intraoperative near-infrared cholangiography&#xD;
      during laparoscopic cholecystectomy has been introduced by Ishizawa et al. in recent years as&#xD;
      a non-invasive, radiation-free, low-cost alternative for realtime visualization of the&#xD;
      biliary anatomy. This technique requires near-infrared laparoscopic imaging systems, as well&#xD;
      as the intravenous injection of a fluorophore, i.e., indocyanine green, which is eliminated&#xD;
      through the biliary tree. Following exposure to the near-infrared fluorescenc light source,&#xD;
      indocyanine green becomes fluorescent and highlights relevant biliary structures. Since the&#xD;
      pioneer studies, a large number of trials have been conducted and several protocols are&#xD;
      currently underway, in order to establish the clinical efficacy of near-infrared&#xD;
      cholangiography. A recent systematic review of clinical studies on near-infrared&#xD;
      cholangiography has reported high visualization rates of biliary structures, as a surrogate&#xD;
      marker of clinical efficacy, before dissection of Calot's triangle. However, one of the most&#xD;
      significant drawbacks of near-infrared cholangiography following systemic indocyanine green&#xD;
      injection lies in the very high background signal due to the rapid accumulation of&#xD;
      indocyanine green in the liver, which can impair the visualization of the biliary structures.&#xD;
&#xD;
      One of the strategies to improve the visualization of the cystic duct and the common bile&#xD;
      duct, without suffering from the disturbing background liver enhancement, is to perform a&#xD;
      near-infrared cholecystocholangiography, by injecting the fluorophore directly into the&#xD;
      gallbladder, as previously demonstrated in a porcine experimental study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 15, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2019</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2019</primary_completion_date>
  <phase>N/A</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Visualization of the cystic duct, common hepatic duct, common bile duct and cysticocholedochal junction.</measure>
    <time_frame>Intra-operatively</time_frame>
    <description>Percentage of patients for whom fluorescence allows visualize cystic duct, common hepatic duct, common bile duct and cysticocholedochal junction with precision. cysticocholedochal junction.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Cholecystectomy</condition>
  <arm_group>
    <arm_group_label>near-infrared cholecystocholangiography</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each subject enrolled in this study will undergo near-infrared cholangiography fluorescence. Once the fundus is grasped and retracted, a needle-tipped cholangiogram catheter is introduced through the skin, adjacent to gallbladder. The catheter, guided by a grasping or dissecting instrument, is used to puncture the infundibulum of the gallbladder. Nine milliliters of bile is aspirated from the gallbladder into a syringe and and a indocianine green solution is injected into the gallbladder. The catheter is removed and the puncture site pinched closed with a grasper. Dissection is then performed under either ambient light or near-infrared mode. The surgical view of the gallbladder dissection is toggled back and forth between the two viewing.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Near-infrared fluorescence cholecystocholangiography</intervention_name>
    <description>Device: Real-Time Fluorescence Imaging (VISERA ELITE II Imaging System). These device is used to identify anatomy, using infrared light that causes the indocianine green to fluoresce.</description>
    <arm_group_label>near-infrared cholecystocholangiography</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Scheduled for elective laparoscopic cholecystectomy.&#xD;
&#xD;
          2. Normal liver and renal function.&#xD;
&#xD;
          3. No hypersensitivity for iodine or indocianine green.&#xD;
&#xD;
          4. Able to understand nature of the study procedures.&#xD;
&#xD;
          5. Willing to participate and with written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Age &lt; 18 years.&#xD;
&#xD;
          2. Liver or renal insufficiency.&#xD;
&#xD;
          3. Known iodine or indocianine green hypersensitivity.&#xD;
&#xD;
          4. Pregnancy or breastfeeding.&#xD;
&#xD;
          5. Not able to understand nature of the study procedure.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hospital Universitario Son Espases</name>
      <address>
        <city>Palma de Mallorca</city>
        <state>Baleares</state>
        <zip>07120</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 16, 2019</study_first_submitted>
  <study_first_submitted_qc>January 19, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 23, 2019</study_first_posted>
  <last_update_submitted>January 23, 2019</last_update_submitted>
  <last_update_submitted_qc>January 23, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Son Espases</investigator_affiliation>
    <investigator_full_name>F Xavier Molina Romero, MD PhD</investigator_full_name>
    <investigator_title>Surgeon</investigator_title>
  </responsible_party>
  <!-- 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/NCT03812432
org study id: XMOL16012019
nct id: NCT03812432
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The objective of this clinical trial is to visualize the bile ducts by injecting a contrast
      that is only visible with infrared light. For this, a quantity of bile will be extracted from
      the gallbladder by puncture and the same amount of contrast will be introduced.

      During the intervention teh tissue wil be exposure to infrared light to visualize the bile
      ducts. This technique aims to increase safety in surgery to avoid damaging bile or vascular
      structures during gallbladder interventions.
Laparoscopic cholecystectomy is one of the most commonly performed procedures in adult
      surgery. A rare but serious complication of laparoscopic cholecystectomy is bile duct injury,
      with a reported incidence of 0.3-1.5 %. Bile duct injury is often caused by misinterpretation
      of the anatomical structures rather than by insufficient technical skills. Generally, bile
      duct injury leads to bile leakage, causing abdominal sepsis. It can also lead to obstruction,
      with obstructive jaundice, eventually potentially leading to a need for liver transplantation
      in the worst case. Late recognition is common in bile duct injuries, resulting in significant
      morbidity and mortality, a lower quality of life and extra costs. A recent expert consensus
      report identified establishment of the critical view of safety as the single most important
      factor for overall safety during laparoscopic cholecystectomy. However, evidence suggests
      that surgeons may actually achieve this view far less often than they believe.

      Numerous intraoperative visualization techniques and technologies have been developed to
      enhance the safety of laparoscopic cholecystectomy. There are mainly two intraoperative
      imaging techniques to consider: first, the historical X-ray-based intraoperative
      cholangiography, and secondly the emerging fluorescence-based intraoperative near-infrared
      cholangiography. Large retrospective and prospective studies have looked at the benefit of
      routine intraoperative radiographic cholangiography for detection of common bile duct stones
      and to identify or prevent bile duct injury. Whether this procedure should be performed
      routinely is still an active subject of debate as systematic reviews are inconclusive;
      however, several of the larger retrospective studies observed a decrease in frequency and
      severity of bile duct injury when intraoperative cholangiography is performed. Limiting
      factors for performing radiographic laparoscopic cholangiography include: it requires
      specific expertise in the technique and its interpretation; it involves the use of ionizing
      radiation; it is time-consuming; and it creates a risk for bile leakage and duct injury
      itself, since puncturing and cannulation of the cystic duct is required. These limitations
      justify the quest for alternative, less complicated techniques to visualize biliary anatomy
      during cholecystectomy. Fluorescence-based intraoperative near-infrared cholangiography
      during laparoscopic cholecystectomy has been introduced by Ishizawa et al. in recent years as
      a non-invasive, radiation-free, low-cost alternative for realtime visualization of the
      biliary anatomy. This technique requires near-infrared laparoscopic imaging systems, as well
      as the intravenous injection of a fluorophore, i.e., indocyanine green, which is eliminated
      through the biliary tree. Following exposure to the near-infrared fluorescenc light source,
      indocyanine green becomes fluorescent and highlights relevant biliary structures. Since the
      pioneer studies, a large number of trials have been conducted and several protocols are
      currently underway, in order to establish the clinical efficacy of near-infrared
      cholangiography. A recent systematic review of clinical studies on near-infrared
      cholangiography has reported high visualization rates of biliary structures, as a surrogate
      marker of clinical efficacy, before dissection of Calot's triangle. However, one of the most
      significant drawbacks of near-infrared cholangiography following systemic indocyanine green
      injection lies in the very high background signal due to the rapid accumulation of
      indocyanine green in the liver, which can impair the visualization of the biliary structures.

      One of the strategies to improve the visualization of the cystic duct and the common bile
      duct, without suffering from the disturbing background liver enhancement, is to perform a
      near-infrared cholecystocholangiography, by injecting the fluorophore directly into the
      gallbladder, as previously demonstrated in a porcine experimental study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Visualization of the cystic duct, common hepatic duct, common bile duct and cysticocholedochal junction.
time frame: Intra-operatively
description: Percentage of patients for whom fluorescence allows visualize cystic duct, common hepatic duct, common bile duct and cysticocholedochal junction with precision. cysticocholedochal junction.
arm group label: near-infrared cholecystocholangiography
arm group type: Experimental
description: Each subject enrolled in this study will undergo near-infrared cholangiography fluorescence. Once the fundus is grasped and retracted, a needle-tipped cholangiogram catheter is introduced through the skin, adjacent to gallbladder. The catheter, guided by a grasping or dissecting instrument, is used to puncture the infundibulum of the gallbladder. Nine milliliters of bile is aspirated from the gallbladder into a syringe and and a indocianine green solution is injected into the gallbladder. The catheter is removed and the puncture site pinched closed with a grasper. Dissection is then performed under either ambient light or near-infrared mode. The surgical view of the gallbladder dissection is toggled back and forth between the two viewing.
intervention type: Device
intervention name: Near-infrared fluorescence cholecystocholangiography
description: Device: Real-Time Fluorescence Imaging (VISERA ELITE II Imaging System). These device is used to identify anatomy, using infrared light that causes the indocianine green to fluoresce.
arm group label: near-infrared cholecystocholangiography
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
facility: 
country: Spain
responsible party type: Principal Investigator
investigator affiliation: Hospital Son Espases
investigator full name: F Xavier Molina Romero, MD PhD
investigator title: Surgeon