Comparison of Icg's Route of Administration During Laparoscopic Cholecystectomy

Choledocholithiasis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04908826
• Other study ID #: 3765/03.02.2020
• Status: Recruiting
• Phase: N/A
• Start date: January 3, 2022
• Est. completion date: January 1, 2023

Study information

• Verified date: March 2022
• Source: Aristotle University Of Thessaloniki
• Contact: Savvas Simeonidis, MD, PhD(c)
• Phone: 698 0309611
• Email: simeonidissavvas[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: January 1, 2023
• Est. primary completion date: June 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Bile Duct Injury
• Cholangiography
• Cholecystolithiasis
• Choledocholithiasis
• Cholelithiasis
• Gallstones
• Indocyanine Green
• Intraoperative Complications
• Post-Op Complication
• Postoperative Complications
• Stone - Biliary

Intervention

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.

Locations

Country	Name	City	State
Greece	General Hospital of Thessaloniki "G. Papanikolaou"	Thessaloniki

Sponsors (2)

Lead Sponsor	Collaborator
Aristotle University Of Thessaloniki	George Papanicolaou Hospital

Country where clinical trial is conducted

Greece, 

References & Publications (9)

Al-Mulhim AA. Current trends in laparoscopic cholecystectomy. J Family Community Med. 1997 Jul;4(2):33-40. — View Citation

Alander JT, Kaartinen I, Laakso A, Pätilä T, Spillmann T, Tuchin VV, Venermo M, Välisuo 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. — View 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. — View Citation

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. — View 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. — View Citation

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. Review. — View Citation

Duca S, Bãlã 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. — View Citation

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. Review. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	operation duration	minutes	intra-operatively
Primary	intra-operative complications (bleeding, bile duct leakage, bile duct injury)	presence or absence	intra-operatively
Primary	applicability of the intra-operatively cholangiography	yes or no	intra-operatively
Primary	presence of bile duct stones (choledocholithiasis)	yes or no	intra-operatively
Secondary	gender	male or female	pre-operatively
Secondary	ASA score	number	pre-operatively
Secondary	age	years	pre-operatively
Secondary	body mass index	kg/m2	pre-operatively
Secondary	indication for laparoscopic cholecystectomy	yes or no	pre-operatively
Secondary	SGOT	g/dL	24 hours prior to surgery and 24 hours after the surgery
Secondary	SGPT	g/dL	24 hours prior to surgery and 24 hours after the surgery
Secondary	ALP	g/dL	24 hours prior to surgery and 24 hours after the surgery
Secondary	?-GT	g/dL	24 hours prior to surgery and 24 hours after the surgery
Secondary	total bilirubin	mg/dL	24 hours prior to surgery and 24 hours after the surgery
Secondary	indirect bilirubin	mg/dL	24 hours prior to surgery and 24 hours after the surgery
Secondary	direct bilirubin	mg/dL	24 hours prior to surgery and 24 hours after the surgery
Secondary	PT	seconds	24 hours prior to surgery and 24 hours after the surgery
Secondary	INR	number	24 hours prior to surgery and 24 hours after the surgery
Secondary	aPTT	seconds	24 hours prior to surgery and 24 hours after the surgery
Secondary	urea	mg/dL	24 hours prior to surgery and 24 hours after the surgery
Secondary	creatinine	mg/dL	24 hours prior to surgery and 24 hours after the surgery
Secondary	CRP	mg/L	24 hours prior to surgery and 24 hours after the surgery
Secondary	WBC	mm3/L	24 hours prior to surgery and 24 hours after the surgery
Secondary	ESR	mm	24 hours prior to surgery and 24 hours after the surgery
Secondary	procalcitonin	mg/dL	24 hours prior to surgery and 24 hours after the surgery
Secondary	TNF-a	pg/ml	24 hours prior to surgery and 24 hours after the surgery
Secondary	IL-6	pg/ml	24 hours prior to surgery and 24 hours after the surgery