Evaluation of Intraoperative Indocyanine Green Fluorescence Angiography for Reducing Anastomotic Leakage in Colorectal Cancer Surgery

The primary objective of this study is to demonstrate that the assessment of **anastomotic perfusion** using intraoperative fluorescence angiography (IOFA) with **indocyanine green** (ICG) will reduce anastomotic leakage (AL) in left-sided or high anterior resection with intraperitoneal anastomosis in patients with **colorectal cancer**. This is clinically relevant as reducing AL can significantly improve surgical outcomes and patient recovery.

Secondary objectives include:

• Assessing the effect of intraoperative fluorescence angiography with ICG on the incidence of change in planned anastomosis during surgery.
• Evaluating the rate of unplanned defunctioning or end stoma.
• Assessing operative and post-operative complications within 90 days of operation, according to the Clavien-Dindo classification.
• Determining the length of post-operative hospital stay.
• Evaluating the rate of reintervention within 90 days.
• Assessing health-related quality of life at baseline and 90 days post-operation using QLQ-C30 and QLQ-CR29 scales.
• Evaluating the medico-economic interest of IOFA with ICG use.
• Assessing the rate of mortality within 90 days.

The clinical trial involves participants diagnosed with **colorectal cancer**. The study population includes both male and female adults over the age of 18, who are scheduled to undergo elective left colectomy or high rectal resection with intraperitoneal anastomosis. Participants must be affiliated with the French social security system, including CMU, and have provided signed informed consent. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of intraoperative fluorescence angiography using **indocyanine green** in reducing anastomotic leakage in patients undergoing colorectal surgery. This is a randomized, single-blind, multicenter phase III trial. The trial is expected to run from September 26, 2022, to December 26, 2025. Participants will be adults scheduled for elective left colectomy or high rectal resection for colorectal cancer with intraperitoneal anastomosis. The primary endpoint is the occurrence of anastomotic leakage within 90 days post-operation, defined by specific clinical criteria.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on inclusion criteria such as age, consent, and social security affiliation. Following the screening, participants will be randomized to receive the intervention. The study involves the administration of **indocyanine green** via intravenous bolus during surgery to assess anastomotic perfusion. Follow-up visits will occur post-surgery to monitor for complications, with assessments at baseline and 90 days post-operation to evaluate health-related quality of life and other secondary endpoints.

The expected duration of participant involvement is approximately 90 days post-surgery. Conditions that may lead to early termination from the study include withdrawal of consent or any adverse events that contraindicate continued participation. The trial aims to provide insights into the medico-economic benefits of using intraoperative fluorescence angiography in colorectal surgery.

The clinical trial involves the use of **Indocyanine Green** as the experimental medication. The product, marketed under the name INFRACYANINE 25 mg/10 mL, is provided in the form of a powder and solvent for solution injectable, which is reconstituted to form a **solution for injection**. The active substance, Indocyanine Green, is of chemical origin and is classified under the ATC code V04CX, indicating its use as a diagnostic agent. The medication is administered via **intravenous bolus use**. The dosing regimen specifies a maximum daily dose of 0.2 mg/kg, with the same amount being the maximum total dose permissible during the treatment period, which is limited to one day. The pharmaceutical product is not formulated for pediatric use and is not classified as an orphan drug.

In addition to the experimental treatment, the study may involve the use of standard-of-care therapies as deemed necessary by the clinical protocol. However, no specific non-experimental treatments, such as placebo or comparator treatments, are explicitly mentioned in the trial data. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol and to assess the efficacy and safety of the treatment regimen.

Efficacy in the clinical trial titled "FLUOCOL-1: Intraoperative Indocyanine Green Fluorescence Angiography in Colorectal Surgery to Prevent Anastomotic Leakage" will be assessed using both primary and secondary endpoints. The primary endpoint is the occurrence of **anastomotic leakage** within 90 days post-operation. Anastomotic leakage is defined as any anastomotic dehiscence with leakage into the pelvic cavity diagnosed upon imaging or at surgical exploration, or any isolated pelvic organ-space infection with no evidence of fistula, as defined by the International Study Group of Rectal Cancer.

Secondary endpoints include several parameters: changes in planned anastomosis during surgery, the rate of defunctioning stoma, overall 90-day postoperative morbidity according to the Clavien-Dindo classification, postoperative mortality within 90 days, duration of hospital stay, postoperative reintervention within 90 days, and health-related quality of life (HRQoL) using the QLQ-C30 and QLQ-CR29 at baseline and 90 days post-operation. Additionally, the medico-economic interest of intraoperative fluorescence angiography (IOFA) with **indocyanine green** (ICG) use will be evaluated. These efficacy parameters will be measured and collected at specified timepoints, including baseline and 90 days post-operation, using validated scales and classifications where applicable.