A randomized, double-blind, single-center trial is currently underway at the Liver Transplantation Center of West China Hospital, Sichuan University, to assess the efficacy and safety of a novel indocyanine green–human serum albumin (ICG-HSA) complex in fluorescence image-guided laparoscopic anatomical liver resection (LALR). The study compares the fluorescence navigation effects of this new ICG-HSA administration scheme with the current guideline-recommended scheme for negative staining in LALR.
Study Design and Population
The prospective trial includes patients aged 18 to 75 years with malignant liver tumors requiring LALR, Child-Pugh class A or B liver disease, and no contraindications to laparoscopic liver resection. Key exclusion criteria include significant cardiopulmonary disease, severe ascites, active bleeding, hepatic encephalopathy, allergy to ICG, or ICG retention rate at 15 minutes of ≥20%. The trial aims to enroll 142 patients, with 71 patients in each group, accounting for an estimated 10% dropout rate.
Intervention: Novel ICG-HSA Complex
The investigational product is a novel ICG-HSA complex developed for fluorescence image-guided LALR. The complex is prepared using commercially available human serum albumin (HSA) and ICG, mixed to achieve a molar ratio of ICG:HSA = 1:6, which was determined to be optimal for clinical use based on in vitro validation experiments. The control group receives a peripheral intravenous injection of 1 mL ICG solution (2.5 mg/mL), while the trial group receives a steady peripheral intravenous infusion of the prepared ICG-HSA complex at a rate of 1 mL/min, administered by a dedicated nurse.
Methodology: Randomization and Blinding
The study employs a customized electronic network central randomization system for block randomization, assigning patients in a 1:1 ratio to either the treatment group (ICG-HSA complex) or the control group (guideline ICG). A double-blind design is implemented, with the surgical team and patients blinded to the group assignments. An opaque curtain covers the anesthesia operation area, and a dedicated research nurse administers the different ICG schemes based on the random numbers.
Primary and Secondary Endpoints
The primary outcome is the effectiveness of intraoperative fluorescence imaging, scored by three independent experts in fluorescence-guided laparoscopic liver resection using a predefined scoring criteria. Secondary endpoints include conversion to open surgery, total operative time, intraoperative blood loss, intraoperative transfusion, tumor resection margins, post-hepatectomy liver failure, length of postoperative hospital stay, incidence of complications (graded by the Clavien–Dindo classification), unplanned reoperation rate, postoperative mortality rate, overall survival time, and disease-free survival time.
Statistical Analysis
Sample size calculation is based on the primary outcome, assuming a mean score difference of 0.5 between the control and experimental groups, with a common standard deviation of 0.8, providing 80% power at a significance level of 0.05. Statistical analysis will be performed using SPSS 26.0 software. Continuous variables will be compared using t-tests or Mann-Whitney U tests, and categorical variables using chi-square or Fisher’s exact tests. Survival analysis will be conducted using the Kaplan-Meier method and log-rank test. Multivariable Cox proportional hazards models will identify independent prognostic factors.
Data Monitoring and Safety
Continuous clinical data monitoring will be performed using an electronic data capture (EDC) system. A data safety monitoring plan is in place, with detailed recording and management of all adverse events. Interim analysis will be performed when 50% of the sample size is enrolled to assess safety and efficacy. Emergency unblinding is permitted if necessary to ensure patient safety.
Ethical Considerations
The study is conducted in accordance with the Declaration of Helsinki and ICH/GCP guidelines. The protocol has been approved by the Ethics Committee of West China Hospital, Sichuan University. All participants provide informed consent and are entitled to withdraw from the study at any time.
This trial aims to determine whether the novel ICG-HSA complex can improve the precision and safety of laparoscopic liver resections, potentially leading to better outcomes for patients with liver tumors.
