Indocyanine green fluorescence for intraoperative detection of liver tumours in minimally invasive surgery: protocol for the LIVERGREEN phase IV multicentre clinical trial

Clinical Snapshot

Key Findings

• P Value: Not applicable - protocol paper

• Effect Size: Not yet available - protocol stage

• Primary Outcome: Impact of preoperative ICG on intraoperative tumour detection rates

• Nnt Or Sensitivity: Sensitivity and specificity of ICG fluorescence detection to be determined

• Confidence Interval: Not specified in protocol

Clinical Application

Requires near-infrared fluorescence imaging systems and standardised ICG protocols ICG is TGA-approved for liver function assessment. Would require PBS consideration for routine surgical use. Relevant to major Australian hepatobiliary centres with laparoscopic capabilities Patients with liver tumours undergoing minimally invasive hepatectomy in tertiary centres

Abstract

INTRODUCTION: Liver tumours are a leading cause of global morbidity and mortality. Current diagnostic tools, including computed tomography (CT), magnetic resonance imaging (MRI) and intraoperative ultrasound (IOUS), have limitations in detecting liver neoplasms. Indocyanine green (ICG) has emerged as a promising tool for improving liver tumour detection. This study aims to assess the impact of preoperative ICG on intraoperative tumour detection in minimally invasive surgery and develop a machine-learning algorithm to enhance tumour detection using ICG fluorescence. METHODS AND ANALYSIS: This prospective, multicentre, phase IV clinical trial adheres to Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. Patients with liver tumours eligible for minimally invasive surgery and a preoperative imaging test will be included. ICG will be administered intravenously 24 hours before surgery. Intraoperative procedures will include IOUS, ICG mapping and photographic documentation. Patients will be followed for 90 days to assess tumour progression, morbidity and mortality. The photographic analysis will enable the development of an artificial intelligence algorithm using machine learning and neural networks to identify lesions based on ICG fluorescence. The estimated sample size is 173 patients and the trial is predicted to accrue in 3 years. ETHICS AND DISSEMINATION: The trial will be conducted in accordance with the Declaration of Helsinki and the Spanish Agency of Medicines and Medical Devices (AEMPS) guidelines. Approved by the local institutional Ethics Committee and the AEMPS, the results will be shared with the scientific community through publications and conferences. EUDRACT NUMBER: 2023-5 08 316-27-00. TRIAL REGISTRATION NUMBER: NCT06398028. PROTOCOL VERSION: V.12, 18 March 2025.

References

1. 1.Huerta, M., Lopez-Ben, S., Lladó, L., Sánchez-Cabús, S., Mils, K., Molina, V., Dopazo, C., Vidal, L., Dalmau, M., Caralt, M., Rosón, N., Merino, X., Armario, D., Salcedo, M. T., Pellino, G., Sapisochin, G., & Gómez-Gavara, C. (2026). Indocyanine green fluorescence for intraoperative detection of liver tumours in minimally invasive surgery: protocol for the LIVERGREEN phase IV multicentre clinical trial. *BMJ Open*, *16*(4), e118275. https://doi.org/10.1136/bmjopen-2026-118275