Indocyanine Green Enhances Intraoperative Detection of Liver Tumors in Imaging-Guided Surgery: A Phase IV Clinical Trial

The primary objective of this phase IV clinical trial is to evaluate the **detection** of liver tumors using indocyanine green (ICG) fluorescence uptake in combination with intraoperative ultrasonography and preoperative Magnetic Resonance Imaging. Additionally, the study aims to develop a machine-learning algorithm to detect liver tumors with ICG by photographic analysis. This is clinically relevant as it may enhance the precision of tumor localization during minimally invasive liver surgery, potentially improving surgical outcomes and reducing recurrence rates.

Secondary objectives include:

• Studying ICG distribution in the liver parenchyma and its correlation with hepatic fibrosis and steatosis.
• Describing ICG uptake patterns and their correlation with liver tumors.
• Analyzing the 30 and 90 days Comprehensive Complication Index, operation time, conversion to open surgery, length of hospital stay, liver tumor recurrence, readmission, and 90-day mortality.

The clinical trial involves **patients with liver tumors** who are scheduled to undergo minimally invasive liver surgery. The study population includes both male and female participants aged 18 years and older. The general health status of the participants is not specified, but they must have an indication for minimally invasive surgery as evaluated by the hospital's multidisciplinary liver tumor board. The total number of participants is not provided by the sponsor. Participants are required to have undergone a contrast-enhanced MRI within six weeks prior to liver surgery. The trial does not include a vulnerable population. Lifestyle considerations such as diet, physical activity, or habits are not detailed in the available data. Key inclusion criteria include the ability to provide consent for data collection and analysis, and the absence of exclusion criteria. The selection process for the trial population is based on these criteria, ensuring that only eligible individuals are included in the study.

The clinical trial is designed to evaluate the efficacy of **indocyanine green** in enhancing the intraoperative detection of liver tumors during imaging-guided surgery. This is a phase IV, randomized, double-blind, controlled trial with an estimated duration from February 2024 to February 2027. The trial aims to analyze the detection of liver tumors using indocyanine green fluorescence uptake in combination with intraoperative ultrasonography and preoperative magnetic resonance imaging. Additionally, the study seeks to develop a machine-learning algorithm to detect liver tumors through photographic analysis.

Participants will be patients with liver tumors who are scheduled for minimally invasive liver surgery, as evaluated by a multidisciplinary liver tumor board. Inclusion criteria include being 18 years or older, having undergone contrast-enhanced MRI within six weeks prior to surgery, and the ability to provide consent for data collection and analysis. The primary endpoint is to quantify the intraoperative detection of liver tumors using intraoperative ultrasonography and indocyanine green.

The trial will involve several study visits, beginning with a screening visit to confirm eligibility based on the inclusion criteria. Participants will then undergo the intervention, which involves the administration of indocyanine green intravenously. Follow-up visits will be scheduled to monitor the participants' response to the intervention and to collect data for the development of the machine-learning algorithm. The end-of-study visit will conclude the trial, where final assessments will be conducted.

Participant involvement is expected to last for the duration of the trial, with the maximum treatment period being one day. Conditions that may lead to early termination from the study include the occurrence of adverse events or withdrawal of consent. The trial is classified as a low-intervention study, meeting all criteria for such classification under RD 1090/2015.

The clinical trial involves the administration of **Indocyanine Green**, a diagnostic drug, to enhance the detection of liver tumors during imaging-guided surgery. **Indocyanine Green** is provided in the form of a **powder for solution for injection**. The active substance, **Indocyanine Green**, is administered intravenously. The dosing regimen specifies a maximum daily dose of 0.2 mg/kg and a maximum total dose of 0.5 mg/kg. The treatment period is limited to a single day. This medication is not formulated for pediatric use and is not classified as an orphan drug.

In addition to the experimental treatment, the study protocol includes the use of standard imaging techniques such as intraoperative ultrasonography and preoperative Magnetic Resonance Imaging (MRI) to assist in the detection of liver tumors. These non-experimental treatments are integral to the study's objective of evaluating the efficacy of **Indocyanine Green** in enhancing tumor detection. Participant compliance with the dosing schedule and administration route will be monitored throughout the trial to ensure adherence to the study protocol.

Efficacy in this clinical trial will be assessed by quantifying the intraoperative detection of liver tumors using intraoperative ultrasonography (IOUS) and **Indocyanine Green** (ICG) fluorescence uptake. The primary endpoint focuses on the ability to detect liver tumors during surgery, leveraging the combination of ICG and IOUS. The trial aims to analyze the detection of liver tumors through ICG fluorescence in conjunction with preoperative Magnetic Resonance Imaging (MRI) and intraoperative ultrasonography. Additionally, a machine-learning algorithm will be developed to enhance tumor detection by analyzing photographic data. The trial is categorized as a Phase IV, low-intervention study, aligning with the criteria set forth in RD 1090/2015. The study is designed to evaluate the efficacy of ICG in improving the visualization of liver tumors during minimally invasive surgical procedures.