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

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.