Clinical trial NCT04908826: Comparison of Icg's Route of Administration During Laparoscopic Cholecystectomy
Official title: Comparison of Administration of Indocyanine Green (ICG) for Image-Guided Laparoscopic Cholocystectomy- A Randomized, Controlled, Prospective Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Laparoscopic; Cholecystectomy
Cholelithiasis; Bile Duct
Choledocholithiasis
Stone - Biliary
Post-Op Complication
Cholangiography
Indocyanine Green
Intraoperative Complications
Bile Duct Injury
Lead sponsor: Aristotle University Of Thessaloniki
Sponsor class: OTHER
Collaborators: name: George Papanicolaou Hospital
First posted: 2021-06-01
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: successful imaging of biliary system
timeFrame: intra-operatively
measure: operation duration
timeFrame: intra-operatively
measure: intra-operative complications (bleeding, bile duct leakage, bile duct injury)
timeFrame: intra-operatively
measure: applicability of the intra-operatively cholangiography
timeFrame: intra-operatively
measure: presence of bile duct stones (choledocholithiasis)
timeFrame: intra-operatively
Secondary outcomes:
measure: gender
timeFrame: pre-operatively
measure: ASA score
timeFrame: pre-operatively
measure: age
timeFrame: pre-operatively
measure: body mass index
timeFrame: pre-operatively
measure: indication for laparoscopic cholecystectomy
timeFrame: pre-operatively
measure: SGOT
timeFrame: 24 hours prior to surgery and 24 hours after the surgery
measure: SGPT
timeFrame: 24 hours prior to surgery and 24 hours after the surgery
measure: ALP
timeFrame: 24 hours prior to surgery and 24 hours after the surgery
measure: γ-GT
timeFrame: 24 hours prior to surgery and 24 hours after the surgery
measure: total bilirubin
timeFrame: 24 hours prior to surgery and 24 hours after the surgery
measure: indirect bilirubin
timeFrame: 24 hours prior to surgery and 24 hours after the surgery
measure: direct bilirubin
timeFrame: 24 hours prior to surgery and 24 hours after the surgery
measure: PT
timeFrame: 24 hours prior to surgery and 24 hours after the surgery
measure: INR
timeFrame: 24 hours prior to surgery and 24 hours after the surgery
measure: aPTT
timeFrame: 24 hours prior to surgery and 24 hours after the surgery
measure: urea
timeFrame: 24 hours prior to surgery and 24 hours after the surgery
measure: creatinine
timeFrame: 24 hours prior to surgery and 24 hours after the surgery
measure: CRP
timeFrame: 24 hours prior to surgery and 24 hours after the surgery
measure: WBC
timeFrame: 24 hours prior to surgery and 24 hours after the surgery
measure: ESR
timeFrame: 24 hours prior to surgery and 24 hours after the surgery
measure: procalcitonin
timeFrame: 24 hours prior to surgery and 24 hours after the surgery
measure: TNF-a
timeFrame: 24 hours prior to surgery and 24 hours after the surgery
measure: IL-6
timeFrame: 24 hours prior to surgery and 24 hours after the surgery
Other outcomes:
Locations:
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki "G. Papanikolaou"
Study officials:
affiliation: General Hospital of Thessaloniki "G. Papanikolaou", Aristotle University of Thessaloniki
name: Savvas Simeonidis, MD, PhD(c)
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
citation: 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.
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