Low Dose ICG for Biliary Tract and Tumor Imaging

Study Overview
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Brief Summary
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Near-infrared fluorescence (NIRF) imaging after an intravenous injection of indocyanine green (ICG) allows for the intraoperative identification of liver anatomy. The investigators have new data that a much lower dose improves this visualization. Confirmation of this hypothesis would mean that ICG can be administered on the same day of surgery in order to augment real-time intraoperative visualization, thereby providing a safe, feasible, and cost-effective strategy for the surgical treatment of liver disease.

Detailed Description
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The investigators have a series of surgical cases in which the investigators have been able to achieve excellent intraoperative biliary visualization with a greatly decreased (50-200 fold lower) dose of ICG than the previously published dose. Furthermore, this decreased dose was visible in about 15-20 minutes from the time of injection with low liver background fluorescence, a significant improvement that would make its utilization in the operating room more practical. The investigators hypothesize that a lower dose will: 1) allow adequate visualization of the extrahepatic biliary tree, including the cystic, common hepatic, and common bile ducts. Confirmation of hypotheses would mean that a lower dose of ICG can be administered on the same day of surgery in order to augment real-time intraoperative localization of the extrahepatic biliary tree, thereby providing a safe, feasible, and cost-effective strategy for the surgical treatment of liver disease. The investigators intend to test our hypothesis with the following specific aims: Aim 1: To compare the efficacy and utility of a low dose ICG (0.05 mg) protocol with a previously published dose (2.5 mg) in imaging the extrahepatic biliary tract.

Official Title
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Low Dose ICG for Near-infrared Fluorescence Imaging of Biliary Tract and Tumors

Conditions
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Cholecystitis, Hepatocellular Carcinoma, Liver Metastases

Intervention / Treatment
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* Drug: Indocyanine green
* Device: PINPOINT Endoscopic Fluorescence


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing standard of care laparoscopic hepatic or biliary operations or Patients undergoing standard of care laparoscopic resection for hepatic tumors: hepatocellular carcinoma or metastatic tumor Exclusion Criteria: Patients with a history of adverse reactions or known allergy to ICG, iodine, or iodine dyes and Pregnant and/or lactating patients.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Adult patients scheduled to undergo a laparoscopic hepatic or biliary operation will be randomized to two groups 1) low dose (0.05 mg) or 2) standard dose (2.5 mg) of ICG preoperatively on the day of surgery. Patients with a history of adverse reactions or known allergy to ICG, iodine, or iodine dyes will be excluded.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Dose<br>Prior to surgery these patients will be given a ICG dose of 0.05 mg IV. | Drug: Indocyanine green<br>* Low dose or standard dose ICG will be administered by the anesthesiologist as guided by the study coordinator at the beginning of the case, at two points during the operation (1- prior to the dissection of the biliary tract and 2- upon completion of the dissection and establishment of the critical view of safety).<br>* Other names: ICG;Device: PINPOINT Endoscopic Fluorescence<br>* The PINPOINT Endoscopic Fluorescence Imaging System (Stryker Corporation, Kalamazoo, Michigan) will be used. This device enables the surgeon to simultaneously see real-time, high-definition visible-range and NIR fluorescence videos and to superimpose them. It is currently approved by the FDA for intraoperative near-infrared fluorescence imaging.<br>* Other names: NIRF;|
| Placebo Comparator: Standard Dose<br>Prior to surgery these patients will be given the ICG standard dose of 2.5 mg IV. | Drug: Indocyanine green<br>* Low dose or standard dose ICG will be administered by the anesthesiologist as guided by the study coordinator at the beginning of the case, at two points during the operation (1- prior to the dissection of the biliary tract and 2- upon completion of the dissection and establishment of the critical view of safety).<br>* Other names: ICG;Device: PINPOINT Endoscopic Fluorescence<br>* The PINPOINT Endoscopic Fluorescence Imaging System (Stryker Corporation, Kalamazoo, Michigan) will be used. This device enables the surgeon to simultaneously see real-time, high-definition visible-range and NIR fluorescence videos and to superimpose them. It is currently approved by the FDA for intraoperative near-infrared fluorescence imaging.<br>* Other names: NIRF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative Assessment - Bile Duct-to-liver Fluorescence Intensity Ratio | Measurement is performed by dividing the fluorescence intensity signal of the common bile duct by that of the liver | intraoperative, average of 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Qualitative Assessment of Overall Intraoperative Visualization of the Extrahepatic Biliary Tree - NIRFC Versus White Light | A qualitative assessment will be made based on the quality of the intraoperative visualization of the extrahepatic biliary tree on a scale of 1 to 5 (1 = no improvement/identification not confirmed; 2 = marginally improved; 3 = sufficiently improved; 4 = well improved; 5 = greatly improved/exceeds expectations). | intraoperative, average of 2 hours | 
| Quantitative Assessment - Bile Duct-to-background Fat Fluorescence Intensity Ratio | Measurement is performed by dividing the fluorescence intensity signal of the common bile duct by that of the background fat | intraoperative, average of 2 hours | 
| Qualitative Assessment of Overall Intraoperative Visualization of the Extrahepatic Biliary Tree (Common Hepatic Duct, Cystic Duct, Common Bile Duct, Aberrant Ducts) | A qualitative assessment will be made based on the quality of the intraoperative visualization of the extrahepatic biliary tree on a scale of 1 to 5 (1 = no improvement/identification not confirmed; 2 = marginally improved; 3 = sufficiently improved; 4 = well improved; 5 = greatly improved/exceeds expectations). | intraoperative, average of 2 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tumors, Biliary Tract, Indocyanine Green (ICG), Near-infrared Fluorescence