Evaluation of Vaginal Slice Vascularization Post-Total Laparoscopic Hysterectomy Using Indocyanine Green Injection: A Prospective Feasibility Study

The primary objective of this study is to evaluate the presence of **indocyanine green** at the level of the vaginal slice during surgical treatment by laparoscopic total hysterectomy. This assessment aims to determine the vascularization of the area intraoperatively, which is clinically relevant for ensuring adequate blood supply and healing post-surgery.

Secondary objectives include:

• Studying the different parameters from the perfusion curve.
• Comparing objective fluorescence measurements with surgeon judgment.
• Evaluating the immediate or delayed tolerance of indocyanine green in the studied context.
• Assessing the time added by the protocol to the total operating time.
• Comparing the vascularization of the vaginal slice according to patient characteristics, surgical technique, type of camera, post-operative complications, and the condition of the vaginal fundus scar.

The clinical trial involves a study population consisting exclusively of **female** participants, as the medical condition under investigation is **total hysterectomy**. The age range of the participants spans from 18 to 64 years, indicating a focus on adult patients. The trial does not include any vulnerable populations. Participants were selected based on the necessity for a hysterectomy that can be performed via laparoscopic surgical treatment. 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 selection criteria emphasize the requirement for adult patients who are candidates for laparoscopic hysterectomy, without further elaboration on additional inclusion or exclusion criteria.

The clinical trial is designed to evaluate the **vascularization** of the vaginal slice following a total laparoscopic hysterectomy using **indocyanine green** injection. This study is a prospective feasibility trial, employing a randomized, double-blind, controlled design to ensure the reliability and validity of the results. The trial is expected to commence on July 1, 2024, and conclude by September 1, 2025, with the total duration of participant involvement being approximately one year. Participants will be adult patients requiring a hysterectomy accessible by laparoscopy, with no specific exclusion criteria outlined.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility is confirmed based on the principal inclusion criteria. Following the screening, participants will undergo the surgical procedure, during which **indocyanine green** is administered intravenously. The primary endpoint is the evolution of green levels in the area of interest, allowing for the generation of a time-fluorescence curve. Secondary endpoints include various parameters derived from the perfusion curve, objective fluorescence measurements, and the surgeon's assessment. The study will also monitor side effects and adverse events related to the injection, as well as the additional time required by the protocol during surgery.

Follow-up visits will be scheduled to assess the vascularization of the vaginal slice, defined by fluorescence intensity values, and to document any post-operative complications. The end-of-study visit will mark the completion of the trial for each participant, ensuring all data is collected and any remaining queries are addressed. Participants may be subject to early termination from the study if they experience significant adverse events or if they withdraw consent. The trial aims to provide valuable insights into the intraoperative evaluation of vascularization, potentially influencing future surgical practices.

The clinical trial involves the use of **INFRACYANINE**, a pharmaceutical product containing the active substance **indocyanine green**. This experimental medication is provided in the form of a powder and solvent for solution injectable, specifically designed for **intravenous administration**. The product is marketed under the name "INFRACYANINE 25 mg/10 mL, poudre et solvant pour solution injectable" and is manufactured by SERB. The maximum daily dose and total dose for the trial are both set at 2 mg/kg, with a maximum treatment period of one day. The primary objective of the trial is to study the presence of indocyanine green at the level of the vaginal slice during surgical treatment by laparoscopic total hysterectomy, to evaluate the vascularization of the area intraoperatively.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The administration of the experimental medication is strictly monitored to ensure participant compliance with the dosing schedule. The trial does not involve any pediatric formulations, and the product is not classified as an orphan drug. The pharmaceutical form of the product is a solution for injection, and it is classified under the ATC code V04CX, which pertains to other diagnostic agents. The chemical origin of the active substance, indocyanine green, is noted, and the product is authorized for use in France.

Efficacy in this clinical trial will be assessed by evaluating the presence and levels of **indocyanine green** at the vaginal slice during laparoscopic total hysterectomy. The primary endpoint involves the evolution of green levels in the area of interest, from which a time-fluorescence curve can be obtained. The presence of fluorescence will be defined by the fluorescence intensity value Fmax-Fmin. Secondary endpoints include various parameters derived from the perfusion curve, such as minimum fluorescence intensity (Fmin), maximum fluorescence intensity (Fmax), the difference in fluorescence intensity (Fmax-min), the slope of the fluorescence intensity, and the time ratio (TR). Objective measurements of fluorescence will be complemented by the surgeon's assessment using a Likert scale.

Additional secondary endpoints will consider the side effects and adverse events associated with the injection of indocyanine green, as well as the time added by the protocol to the total operating time. The vascularization of the vaginal slice will be analyzed based on fluorescence intensity values (Fmax-Fmin) in relation to patient characteristics, surgical techniques, camera types, and post-operative complications. The study will also evaluate the condition of the vaginal fundus scar. These assessments will be conducted intraoperatively and during the post-operative consultation, ensuring a comprehensive evaluation of the efficacy of indocyanine green in assessing vascularization during the surgical procedure.