Comparison of Icg's Route of Administration During Laparoscopic Cholecystectomy

Comparison of Administration of Indocyanine Green (ICG) for Image-Guided Laparoscopic Cholocystectomy- A Randomized, Controlled, Prospective Trial

The aim of the trial is to compare the routes of administration of indocyanine green (ICG) during laparoscopic cholocystectomy.

Study Overview

• Status: Recruiting
• Conditions: Intraoperative Complications; Choledocholithiasis; Post-Op Complication; Indocyanine Green; Bile Duct Injury; Stone - Biliary; Laparoscopic; Cholecystectomy; Cholelithiasis; Bile Duct; Cholangiography
• Intervention / Treatment: Procedure: Indocyanine Green (ICG) administration

Detailed Description

Laparoscopic cholecystectomy is now the method of choice for the treatment of symptomatic and complicated gallstones.

There are two major problems that can occur during and after a laparoscopic cholecystectomy. These are the remaining stones in the bile duct and the iatrogenic injuries of the bile ducts. Iatrogenic bile duct injuries are the most difficult complication of cholecystectomy and are a clinical entity that needs multifactorial treatment as it significantly increases morbidity, mortality and overall cost. Intraoperative cholangiography is used to prevent these complications.

Intraoperative cholangiography is the traditional method of identifying bile duct anatomy during laparoscopic cholecystectomy. This method has the disadvantages that both the patient and the staff are exposed to radiation, while in order to perform it, catheterization of the cystic duct must be performed, which requires surgical procedures that increase the time of the operation, while in some cases it is not technically easy. Finally, with the intraoperative cholangiography, the injuries of the bile ducts are detected, after they have taken place, therefore it helps in their timely diagnosis but does not limit the frequency of their occurrence.

Indocyanine green is a sterile, anionic, water-soluble but relatively hydrophobic tricarbocyanine molecule with a molecular weight of 751.4. It was developed in 1955 at Kodak Laboratories and in 1959 was approved for clinical use by the FDA. It has the property of fluorescing, after its administration, with a maximum absorption at 800 nm after exposure to infrared lighting. Its use offers an image of high clarity and sensitivity, target imaging, with parallel low acoustic emission. Indocyanine green has the following properties and advantages, which make it an important tool in the applications of medical sciences and studies.

Following intravenous administration, it binds to plasma lipoproteins with minimal escape into the interstitial space. Extremely important for its clinical use is the complete excretion through the bile, as well as the non-production of metabolic products. It has low toxicity in the absence of ionization, which in combination with the short half-life of the substance, provides safety for the patient in its use and application in medical and biomedical sciences. It has low costs that in combination with its ease of use facilitates its application. No expensive equipment or large learning curve required. Also the possibility of recurrence with re-administration intraoperatively can offer a number of applications in laparoscopic surgery. It has a low rate of side effects and interactions with other drugs and preparations, a major allergic reaction has been reported in the literature. The first clinical applications of indocyanine green were to assess cardiac function, liver function in cirrhotic patients before hepatectomy, and to examine the retinal vessels.

Its use in laparoscopic cholecystectomy, as already mentioned, is based on its ability to fluoresce when exposed to infrared light and in combination with the fact that when administered intravenously it is concentrated and excreted from the bile offers the possibility of intraoperative, fluorescent cholangiography that aims to identify the elements of the Callot triangle.

This study aims to demonstrate that endocyanin green cholangiography is equivalent to or better than conventional cholangiography for the diagnosis of cholelithiasis and biliary injuries. It is therefore an important clinical application that will probably facilitate surgeons both in the prevention of biliary injuries and in the intraoperative diagnosis of cholelithiasis.

Patients who will undergo laparoscopic cholecystectomy will be randomly divided into 3 (three) groups. The processing of the results will be done in the appropriate way and method. A total of 240 patients will be randomized into three groups of 80. In the first group (A) classical cholangiography will be performed. In group (B) will be performed intravenous fluorescent cholangiography with indocyanine green 6 (six) hours before the start of surgery. In the third group (C) will be performed intraoperative cholangiography with direct administration of indocyanine green to the gallbladder.

• Study Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Savvas Simeonidis, MD, PhD(c); Phone Number: 0030 698 0309611; Email: simeonidissavvas@yahoo.com
• Study Contact Backup: Name: Panagiotis Christidis, MD, MSc; Phone Number: 0030 6940730227; Email: panagiotischristidis13@gmail.com

Study Locations

• Greece
  • Thessaloniki, Greece, 57010
    • Recruiting
    • General Hospital of Thessaloniki "G. Papanikolaou"
    • Contact: Savvas Simeonidis, MD, PhD(c)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. age older than 18 years old
2. laparoscopic cholecystectomy
3. elective surgery

Exclusion Criteria:

1. younger than 18 years old
2. no consent to participate to the study
3. history of allergic reaction to iodine products
4. urgent or emergent cholecystectomy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A (standard cholangiography during surgery); All patients will undergo laparoscopic cholecystectomy. In this group standard cholangiography will be performed during surgery. Standard cholangiography will be performed with selective catheterization of the cystic duct and infusion of a radiolucent substance (non-ionic low osmotic iodine). The category includes drugs such as iohexol, iopamidol, iopromide, ioversol, iobitriol, iomeprol and iodixanol. In our study we will use Xenetix (iobitriol) and perform cholangiography with C-ARM recording.	Procedure: Indocyanine Green (ICG) administration; Patients will undergo laparoscopic cholecystectomy after they are randomly divided into 3 (three) groups. A total of 240 patients will be randomized into three groups of 80. In the first group (A) standard cholangiography will be performed. In group (B) intravenous fluorescent cholangiography with indocyanine green will be performed during surgery. ICG at a dose of 0.3 mg / mL / Kg 6 (six) hours prior to surgery will be administered. In the third group (C), intraoperative cholangiography will be performed with direct administration of indocyanine green at a dose of 0.03 mg / ml / Kg to the gallbladder.; Other Names: laparoscopic cholecystectomy; intra-operative cholangiography; c-arm recording; iodine solution administration
Active Comparator: Group B (cholangiography with iv administration of icg prior to surgery); All patients will undergo laparoscopic cholecystectomy. In this group intravenous fluorescent cholangiography with indocyanine green will be given at a dose of 0.3 mg / mL / Kg 6 (six) hours before the start of surgery.The bile duct system will be recorded with a special camera (Karl Storz NIR / ICG).	Procedure: Indocyanine Green (ICG) administration; Patients will undergo laparoscopic cholecystectomy after they are randomly divided into 3 (three) groups. A total of 240 patients will be randomized into three groups of 80. In the first group (A) standard cholangiography will be performed. In group (B) intravenous fluorescent cholangiography with indocyanine green will be performed during surgery. ICG at a dose of 0.3 mg / mL / Kg 6 (six) hours prior to surgery will be administered. In the third group (C), intraoperative cholangiography will be performed with direct administration of indocyanine green at a dose of 0.03 mg / ml / Kg to the gallbladder.; Other Names: laparoscopic cholecystectomy; intra-operative cholangiography; c-arm recording; iodine solution administration
Active Comparator: Group C (cholangiography with direct administration of icg to the bile duct system during surgery); All patients will undergo laparoscopic cholecystectomy. In the third group intraoperative cholangiography will be performed with direct administration of indocyanine green at a dose of 0.03 mg / ml / Kg to the bile duct cyst.	Procedure: Indocyanine Green (ICG) administration; Patients will undergo laparoscopic cholecystectomy after they are randomly divided into 3 (three) groups. A total of 240 patients will be randomized into three groups of 80. In the first group (A) standard cholangiography will be performed. In group (B) intravenous fluorescent cholangiography with indocyanine green will be performed during surgery. ICG at a dose of 0.3 mg / mL / Kg 6 (six) hours prior to surgery will be administered. In the third group (C), intraoperative cholangiography will be performed with direct administration of indocyanine green at a dose of 0.03 mg / ml / Kg to the gallbladder.; Other Names: laparoscopic cholecystectomy; intra-operative cholangiography; c-arm recording; iodine solution administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
successful imaging of biliary system	The anatomy of the extrahepatic bile ducts will be orally determined by the surgeon and the cases in which the oral description will coincide with the findings of cholangiography or not and where there were differences will be recorded.	intra-operatively
operation duration	minutes	intra-operatively
intra-operative complications (bleeding, bile duct leakage, bile duct injury)	presence or absence	intra-operatively
applicability of the intra-operatively cholangiography	yes or no	intra-operatively
presence of bile duct stones (choledocholithiasis)	yes or no	intra-operatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
gender	male or female	pre-operatively
ASA score	number	pre-operatively
age	years	pre-operatively
body mass index	kg/m2	pre-operatively
indication for laparoscopic cholecystectomy	yes or no	pre-operatively
SGOT	g/dL	24 hours prior to surgery and 24 hours after the surgery
SGPT	g/dL	24 hours prior to surgery and 24 hours after the surgery
ALP	g/dL	24 hours prior to surgery and 24 hours after the surgery
γ-GT	g/dL	24 hours prior to surgery and 24 hours after the surgery
total bilirubin	mg/dL	24 hours prior to surgery and 24 hours after the surgery
indirect bilirubin	mg/dL	24 hours prior to surgery and 24 hours after the surgery
direct bilirubin	mg/dL	24 hours prior to surgery and 24 hours after the surgery
PT	seconds	24 hours prior to surgery and 24 hours after the surgery
INR	number	24 hours prior to surgery and 24 hours after the surgery
aPTT	seconds	24 hours prior to surgery and 24 hours after the surgery
urea	mg/dL	24 hours prior to surgery and 24 hours after the surgery
creatinine	mg/dL	24 hours prior to surgery and 24 hours after the surgery
CRP	mg/L	24 hours prior to surgery and 24 hours after the surgery
WBC	mm3/L	24 hours prior to surgery and 24 hours after the surgery
ESR	mm	24 hours prior to surgery and 24 hours after the surgery
procalcitonin	mg/dL	24 hours prior to surgery and 24 hours after the surgery
TNF-a	pg/ml	24 hours prior to surgery and 24 hours after the surgery
IL-6	pg/ml	24 hours prior to surgery and 24 hours after the surgery

Collaborators and Investigators

• Sponsor: Aristotle University Of Thessaloniki
• Collaborators: George Papanicolaou Hospital
• Investigators: Principal Investigator: Savvas Simeonidis, MD, PhD(c), General Hospital of Thessaloniki "G. Papanikolaou", Aristotle University of Thessaloniki

Publications and helpful links

General Publications

• Boni L, David G, Mangano A, Dionigi G, Rausei S, Spampatti S, Cassinotti E, Fingerhut A. Clinical applications of indocyanine green (ICG) enhanced fluorescence in laparoscopic surgery. Surg Endosc. 2015 Jul;29(7):2046-55. doi: 10.1007/s00464-014-3895-x. Epub 2014 Oct 11.
• Duncan CB, Riall TS. Evidence-based current surgical practice: calculous gallbladder disease. J Gastrointest Surg. 2012 Nov;16(11):2011-25. doi: 10.1007/s11605-012-2024-1. Epub 2012 Sep 18.
• Alander JT, Kaartinen I, Laakso A, Patila T, Spillmann T, Tuchin VV, Venermo M, Valisuo P. A review of indocyanine green fluorescent imaging in surgery. Int J Biomed Imaging. 2012;2012:940585. doi: 10.1155/2012/940585. Epub 2012 Apr 22.
• Costi R, Gnocchi A, Di Mario F, Sarli L. Diagnosis and management of choledocholithiasis in the golden age of imaging, endoscopy and laparoscopy. World J Gastroenterol. 2014 Oct 7;20(37):13382-401. doi: 10.3748/wjg.v20.i37.13382.
• Duca S, Bala O, Al-Hajjar N, Lancu C, Puia IC, Munteanu D, Graur F. Laparoscopic cholecystectomy: incidents and complications. A retrospective analysis of 9542 consecutive laparoscopic operations. HPB (Oxford). 2003;5(3):152-8. doi: 10.1080/13651820310015293.
• Al-Mulhim AA. Current trends in laparoscopic cholecystectomy. J Family Community Med. 1997 Jul;4(2):33-40.
• Ambe PC, Plambeck J, Fernandez-Jesberg V, Zarras K. The role of indocyanine green fluoroscopy for intraoperative bile duct visualization during laparoscopic cholecystectomy: an observational cohort study in 70 patients. Patient Saf Surg. 2019 Jan 12;13:2. doi: 10.1186/s13037-019-0182-8. eCollection 2019.
• Chu W, Chennamsetty A, Toroussian R, Lau C. Anaphylactic Shock After Intravenous Administration of Indocyanine Green During Robotic Partial Nephrectomy. Urol Case Rep. 2017 Mar 10;12:37-38. doi: 10.1016/j.eucr.2017.02.006. eCollection 2017 May.
• Hope-Ross M, Yannuzzi LA, Gragoudas ES, Guyer DR, Slakter JS, Sorenson JA, Krupsky S, Orlock DA, Puliafito CA. Adverse reactions due to indocyanine green. Ophthalmology. 1994 Mar;101(3):529-33. doi: 10.1016/s0161-6420(94)31303-0.

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2022
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: May 10, 2021
• First Submitted That Met QC Criteria: May 26, 2021
• First Posted (Actual): June 1, 2021

Study Record Updates

• Last Update Posted (Actual): March 10, 2022
• Last Update Submitted That Met QC Criteria: March 9, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Pathological Conditions, Anatomical; Gallbladder Diseases; Biliary Tract Diseases; Bile Duct Diseases; Common Bile Duct Diseases; Calculi; Postoperative Complications; Gallstones; Cholelithiasis; Cholecystolithiasis; Choledocholithiasis; Intraoperative Complications
• Other Study ID Numbers: 3765/03.02.2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No