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

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.

Conditions

• Laparoscopic Cholecystectomy Surgery

Interventions

DRUG

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.

DRUG

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.

Sponsors & Collaborators

• Spanish Association of Surgeons (AEC)

  collaborator OTHER

• Instituto de Investigación Biomédica de Salamanca

  lead OTHER

Principal Investigators

• Jaime López, Medical Degree in Surgery · Centro Asistencial Universitario de Salamanca (CAUSA)

• Eva Alonso · Complejo Asistencial de Zamora.

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-02-26

Primary Completion

2026-11-15

Completion

2027-01-31

Countries

• Spain

Study Locations