Fluorescent Cholangiography vs White Light for Bile Ducts Identification

Efficacy Of Near Infrared Incisionless Fluorescent Cholangiography (NIFC) During Laparoscopic Cholecystectomy

The Study is designed to compare the effectiveness of Near Infrared Fluorescence Cholangiography (NIFC) to standard white light imaging (WLI) in visualizing and identifying the main biliary and hepatic structures (Cystic Duct, Right Hepatic Duct, Common Hepatic Duct, Common Bile Duct, Cystic-CBD junction, Cystic-Gallbladder junction and any Accessory Ducts) during laparoscopic cholecystectomy. The aim is to demonstrate that NIFC performs better than standard white light (WLI) alone in visualizing and identifying extra-hepatobiliary structures (Cystic Duct, Right Hepatic Duct, Common Hepatic Duct, Common Bile Duct, Cystic-CBD junction, Cystic-Gallbladder junction, and any Accessory Ducts) before and after dissection during Laparoscopic Cholecystectomy (LC).

Study Overview

• Status: Completed
• Conditions: Cholecystitis; Cholelithiasis
• Intervention / Treatment: Procedure: Laparoscopic cholecystectomy with Xenon light; Procedure: Laparoscopic cholecystectomy (fluorescent cholangiography)

Detailed Description

Recently, a novel technique to visualize structures using fluorescent light and intravenous dye has been developed.

Near Infrared Incisionless Fluorescent Cholangiography (NIFC) is a medical imaging technique that uses fluorescence to detect properly labeled structures during surgery.

NIFC is performed using imaging devices with the purpose of providing real-time simultaneous information from color reflectance images (white light) and fluorescence emission (near infrared light). One or more light sources are used to excite and illuminate the sample. Light is collected using optical filters that match the emission spectrum of the fluorophore. Imaging lenses and digital cameras are used to produce the final image.

During laparoscopic cholecystectomies, the visualization of the extra-hepatic bile ducts with fluorescence is called Near Infrared Incisionless Fluorescent Cholangiography (NIFC). Fluorescence equipment and a dye are necessary in order to perform a NIFC, but the technique requires no radiation or incision. A fluorescence dye is administrated intravenously at least 45 minutes before the surgery, which is excreted by the liver and the bile duct The Study is designed to compare the effectiveness of Near Infrared Fluorescence Cholangiography (NIFC) to standard white light imaging (WLI) in visualizing and identifying the main biliary and hepatic structures (Cystic Duct, Right Hepatic Duct, Common Hepatic Duct, Common Bile Duct, Cystic-CBD junction, Cystic-Gallbladder junction and any Accessory Ducts) during laparoscopic cholecystectomy.

Eligible patients will be identified through clinical and test evaluation. Eligibility will be verified by the patient's primary surgeon. The surgeon will determine the indication and date of the surgery. Once a patient is confirmed as eligible, the surgeon will introduce the study in detail. If after being introduced to the study and having had the opportunity to ask questions, the patient is willing to participate, he/she will be asked to review and sign the informed consent document .

Upon entry in the clinical trial patients will be randomly allocated to the intervention arm. Data will be collected at enrolment time, during surgery, at the end of surgery and one week after surgery.

Upon entry in the clinical trial, the master study database (REDCap, will randomly allocated patients to one of the study arms (1:1) within site (1:1) using a computer generated random sequence. This will provide an allocation sequence for each site. Once a patient is enrolled and a database file in REDCap is initiated for that patient, he/she will be assigned electronically to one of the study arms.

Patient will be blind to the intervention but surgeon blinding will not be feasible due to the nature of the intervention. The study will involve a considerable number of surgeons in each site, which should compensate any potential bias of some of them in favor or against either approach.

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • HOSPITAL DE CLINICAS JOSE DE SAN MARTIN
• Germany
  • Hamburg, Germany
    • Askelopios Westklinikum Hamburg
  • Rostock, Germany
    • Klinikum Südstadt Rostock
• Italy
  • Varese, Italy
    • University of Insubria
• Japan
  • Tokyo, Japan
    • University of Tokyo
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedar Sinai
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients of both genders
2. Minimum age: 18 years old
3. Spoken and written command of the language spoken in the country's center
4. Ability to understand and follow the study procedures and sign the informed consent

Exclusion Criteria:

1. Known allergies to iodides
2. Known history of coagulopathy
3. Known moderate or severe liver disease Women who are pregnant or breastfeeding, or for whom possibility of pregnancy was not ruled out

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Xenon Light; Laparoscopic cholecystectomy with Xenon Light	Procedure: Laparoscopic cholecystectomy with Xenon light; Standard laparoscopic cholecystectomy with white light
EXPERIMENTAL: Near infrared light; Laparoscopic cholecystectomy with Near infrared light	Procedure: Laparoscopic cholecystectomy with Xenon light; Standard laparoscopic cholecystectomy with white light; Procedure: Laparoscopic cholecystectomy (fluorescent cholangiography); Laparoscopic cholecystectomy in infrared light after injection of indocyanine green pre-operatively.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection Rate of extra-hepatobiliary structures using near infra-red light	Detection Rate of each particular extra-hepatobiliary structure during Laparoscopic Cholecystectomy defined as the total number of patients in which the particular structure is detected before and after dissection in that arm of the Study, divided by the total number of patients in that arm.	One year

Collaborators and Investigators

• Sponsor: The Cleveland Clinic
• Collaborators: Cedars-Sinai Medical Center; Asklepios Kliniken Hamburg GmbH; Università degli Studi dell'Insubria; University of Rostock; Tokyo Medical University; Hospital de Clinicas José de San Martín
• Investigators: Principal Investigator: Raul Rosenthal, MD, Cleveland Clinic Florida

Publications and helpful links

General Publications

• Dip F, LoMenzo E, Sarotto L, Phillips E, Todeschini H, Nahmod M, Alle L, Schneider S, Kaja L, Boni L, Ferraina P, Carus T, Kokudo N, Ishizawa T, Walsh M, Simpfendorfer C, Mayank R, White K, Rosenthal RJ. Randomized Trial of Near-infrared Incisionless Fluorescent Cholangiography. Ann Surg. 2019 Dec;270(6):992-999. doi: 10.1097/SLA.0000000000003178.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2016
• Primary Completion (ACTUAL): December 31, 2017
• Study Completion (ACTUAL): August 31, 2018

Study Registration Dates

• First Submitted: February 17, 2016
• First Submitted That Met QC Criteria: March 3, 2016
• First Posted (ESTIMATE): March 9, 2016

Study Record Updates

• Last Update Posted (ACTUAL): April 22, 2019
• Last Update Submitted That Met QC Criteria: April 18, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathological Conditions, Anatomical; Gallbladder Diseases; Biliary Tract Diseases; Calculi; Cholecystitis; Gallstones; Cholelithiasis; Cholecystolithiasis; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Anesthetics, Inhalation; Xenon
• Other Study ID Numbers: FLA 15-108

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Redcap will be used Data to be shared - pre-operative data including age, sex, laboratory values and imaging, intra-operative data including visualization of the extra-hepatic biliary structure with white light and with infrared light by the operating surgeon and the observer, any bile leak; post-operative data documenting any complications such as reaction to ICG or bile duct injury.

Data will be available as each center finishes up the follow of each individual patient (usually 2 weeks post operatively). Each center will update the data on Redcap on a monthly basis.

Data will be initially obtained on a pre-decided forms (approved by the IRB committee) and transferred to Redcap for electronic record keeping and analysis.