Comparison Between Standard and Reduced Doses of Indocyanine Green in Fluorescence Cholangiography During Laparoscopic Cholecystectomy.

Condition(s) studied

Investigational drug(s) / intervention(s)

Intravenous injection of indocianine green at least three hours before surgery at a dose of 2.5 mg per subject.: A dilution will be prepared by dissolving 25 mg of ICG in 10 mL of water for injectable solutions, yielding a concentration of 2.5 mg/mL. Once the solution is prepared, 1 mL will be administered directly via a peripheral venous line in the patient's upper limb.

Intravenous injection of indocianine green 15 to 30 minutes before surgery at a dose of 0.25 mg per subject.: A dilution will be prepared by dissolving 25 mg of ICG in 25 mL of water for injectable solutions, yielding a concentration of 1 mg/mL. Subsequently, 0.25 mL will be administered as a direct intravenous injection via a peripheral venous line in the patient's upper limb.

Study summary

Introduction:

This protocol outlines a randomized phase IV clinical trial designed to compare the efficacy of two different doses of indocyanine green (ICG) used in near-infrared fluorescent cholangiography during laparoscopic cholecystectomy (LC)-the current gold standard treatment for symptomatic cholelithiasis. Despite its effectiveness, LC is still associated with significant risks, particularly bile duct injury (BDI), a severe complication that this study aims to mitigate.

Phase: Phase IV Study design: Multicenter, randomized, open-label, parallel-group clinical trial (modified intention-to-treat).

Objectives:

Primary objective:

* To analyze differences between treatment groups (standard dose 2.5 mg \>3h preoperative vs reduced dose 0.25 mg immediate preoperative 15-30 min) during laparoscopic cholecystectomy in:
* Visualization of extrahepatic biliary structures
* Degree of visualization
* Degree of background liver fluorescence interference
* Perceived utility of the technique

Secondary objectives:

* Influence of BMI, biliary pathology type, surgery type, prior inflammation, surgical difficulty, previous instrumentation, and laparoscopic imaging system on results
* Intraoperative and postoperative complication rates
* 30-day mortality
* Impact on operative time and hospital stay
* Correlation between subjective and objective fluorescence assessment (ducts-to-liver fluorescence ratio) Population: Patients ≥18 years indicated for laparoscopic cholecystectomy (elective, early or urgent deferred).

Main inclusion criteria:

* Age ≥18 years
* Signed informed consent
* Indication for laparoscopic cholecystectomy (symptomatic cholelithiasis, gallbladder polyps with surgical indication)

Main exclusion criteria:

* Age \<18 years
* Pregnancy or lactation
* Chronic kidney disease (stage \>IIIb)
* ICG or iodinated contrast allergy
* Functional thyroid disease
* Emergency non-deferrable surgery
* Open approach
* Suspicion of gallbladder carcinoma
* Inability to understand the study Investigational product: Indocyanine green (ICG), intravenous administration

This multicenter study involves two hospitals in Castilla y León, Spain, and plans to enroll 122 adult patients meeting specific clinical criteria for LC. Participants will be randomized into two treatment arms and will receive ICG accordingly:

* Group 1: 2.5 mg \>3h before surgery
* Group 2: 0.25 mg 15-30 min before surgery Fluorescence will be assessed both subjectively by the surgical team and objectively through digital image analysis using specialized software to calculate the bile duct-to-liver fluorescence ratio (RFBH).

Endpoints:

* Rates and degree of biliary structure identification pre- and post-dissection
* Perceived utility of cholangiography
* Liver background fluorescence interference
* Ducts-to-liver fluorescence ratio Duration: 12 months recruitment + 1 month follow-up = total 13 months Countries: Spain Ethics: The study will be conducted in accordance with ICH-GCP, EU Clinical Trials Regulation No 536/2014, and applicable national regulations.

Beyond comparing the diagnostic performance of two dosing strategies, this study seeks to provide evidence supporting a more practical and logistically feasible approach for implementing ICG fluorescence cholangiography in routine surgical practice, without compromising diagnostic accuracy or patient safety.

Eligibility

Primary outcome measure(s)

• Identification of biliary structures prior to dissection of the hepatocystic triangle. — During surgery
  The identification of extrahepatic biliary structures prior to the dissection of the hepatocystic triangle is defined as the visualization of fluorescence emitted by these structures during laparoscopic surgery, at a minimum distance of 15 cm from the anatomical structure and with a perpendicular orientation of the laparoscopic optics to it. The following scale will be used: Category 1. Identification of the cystic duct prior to dissection Category 2. Identification of the common bile duct prior to dissection Category 3. Identification of the junction of the cystic duct with the common bile duct prior to dissection Category 4. Identification of the union of the cystic duct with the gallbladder prior to dissection Category 5. Identification of the common hepatic duct prior to dissection Category 6. Identification of biliary anatomical variables prior to dissection.
• Identification rate of biliary structures after dissection of the hepatocystic triangle — During surgery.
  The identification of extrahepatic biliary structures after dissection of the hepatocystic triangle is defined as the visualization of fluorescence emitted by these structures during laparoscopic surgery, at a minimum distance of 15 cm from the anatomical structure and with a perpendicular orientation of the laparoscopic optics over it. The following scale will be used: Category 1. Identification of the cystic duct after the dissection Category 2. Identification of the common bile duct after the dissection. Category 3. Identification of the junction of the cystic duct with the common bile duct after the dissection Category 4. Identification of the union of the cystic duct with the gallbladder after the dissection Category 5. Identification of the common hepatic duct after the dissection Category 6. Identification of biliary anatomical variables after the dissection.
• Degree of identification of extrahepatic biliary structures prior to dissection of the hepatocystic triangle — During surgery
  The degree of identification of extrahepatic biliary structures is assessed using a 3-point Likert scale: Poor (1): unable to distinguish fluorescence in extrahepatic biliary structures. Good (2): able to visualize fluorescence at least in the main bile duct. Excellent (3): able to visualize fluorescence in the main bile duct, the cystic duct, and their junction. The assessment of this variable must be performed before any surgical maneuver within the hepatocystic triangle.
• Degree of identification of extrahepatic biliary structures after dissection of the hepatocystic triangle — During surgery.
  The degree of identification of extrahepatic biliary structures is assessed using a 3-point Likert scale: Poor (1): unable to distinguish fluorescence in extrahepatic biliary structures. Good (2): able to visualize fluorescence at least in the main bile duct. Excellent (3): able to visualize fluorescence in the main bile duct, the cystic duct, and their junction. The assessment of this variable must be performed before any surgical maneuver within the hepatocystic triangle.
• Perceived usefulness of fluorescence cholangiography (FC). — During surgery
  The usefulness of FC during surgery is assessed using a 3-point Likert scale: Not useful (1): the technique did not provide any benefit or even hindered the procedure. Moderately useful (2): the technique guided certain phases of the procedure. Very useful (3): the technique guided most phases of the procedure, assisted decision-making, or even modified a previous surgical decision.
• Degree to which background liver fluorescence (contrast between the liver and biliary ducts) was perceived as disturbing — During surgery
  The disturbing effect of background liver fluorescence is assessed using a 3-point Likert scale: None (0): liver fluorescence was almost imperceptible and/or allowed clear visualization of hepatocystic triangle structures before dissection. Slightly disturbing (1): liver fluorescence was evident but still allowed clear visualization of hepatocystic triangle structures after dissection. Very disturbing (2): liver fluorescence was significantly disturbing and prevented identification of extrahepatic biliary anatomy either before or after dissection of the hepatocystic triangle.

Trial sites (2)

More Instituto de Investigación Biomédica de Salamanca trials in Spain