Intraoperative Indocyanine Green Fluorescence Angiography in Colorectal Surgery to Prevent Anastomotic Leakage — FLUOCOL-1  

Colorectal Cancer Clinical Trial

Official title: Intraoperative Indocyanine Green Fluorescence Angiography in Colorectal Surgery to Prevent Anastomotic Leakage: a Single-blind Phase III Multicenter Randomized Controlled Trial (Intergroup FRENCH-GRECCAR Trial)

Status Recruiting

Clinical Trial Summary

Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer in the world and the third in France. Its incidence is steadily rising in developing nations. Anastomotic leak (AL) is a major problem in colorectal surgery affecting at least 7% of patients operated on for left colonic cancer. It is the most feared complication after colorectal anastomosis, associated with mortality, prolonged hospitalization, impaired health related quality of life (HRQoL) and increased health care costs. Intraoperative fluorescence angiography (IOFA) with indocyanine green (ICG) may help preventing AL. Available studies on the effects of IOFA with ICG are heterogeneous and randomized controlled trial are scarce. Our aim is to demonstrate that IOFA with ICG could lead to a reduction of AL rate after left-sided or low anterior resection with anastomosis for CRC.

The FLUOCOL-1 study is the first national, multicenter, single blind, randomized, 2-arm, phase III superiority clinical trial. The primary endpoint is the occurrence of an AL 90 days post-operation. AL 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.

The study population will be made of adult patients with left-sided or high rectal cancer scheduled to undergo elective left colectomy or high rectal resection (by open, laparoscopy or robotic surgery) and with expected stapled or hand-sewn intraperitoneal anastomosis. The exclusion criteria are mainly an emergent surgery; rectal cancer requiring total mesorectal excision and anastomosis expected below the peritoneal reflection; CRC requiring total or subtotal colectomy; CRC requiring transverse colectomy; recurrent CRC and locally advanced colorectal cancer requiring multi-visceral excision.

A total of 1010 patients will be necessary (39 patients in each centre during 36 months). An interim analysis for efficacy and futility is scheduled when half of the participants will have been recruited.

In case of positive results favoring IOFA, this study would define the use of IOFA as a standard of care in colorectal surgery. At the patient level, a significantly lower rate of AL will reduce hospital stay and stoma rate, and will ensure improved postoperative recovery, faster return to normal activity and better long-term oncologic outcomes.

Clinical Trial Description

Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer in the world and the third in France. Its incidence is steadily rising in developing nations. Anastomotic leak (AL) is a major problem in colorectal surgery affecting at least 7% of patients operated on for left colonic cancer. It is the most feared complication after colorectal anastomosis, associated with mortality, prolonged hospitalization, impaired health related quality of life (HRQoL) and increased health care costs. Intraoperative fluorescence angiography (IOFA) with indocyanine green (ICG) may help preventing AL. Available studies on the effects of IOFA with ICG are heterogeneous and randomized controlled trial are scarce. Our aim is to demonstrate that IOFA with ICG could lead to a reduction of AL rate after left-sided or low anterior resection with anastomosis for CRC.

The FLUOCOL-1 study is the first national, multicenter, single blind, randomized, 2-arm, phase III superiority clinical trial. The primary endpoint is the occurrence of an AL 90 days post-operation. AL 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.

The study population will be made of adult patients with left-sided or high rectal cancer scheduled to undergo elective left colectomy or high rectal resection (by open, laparoscopy or robotic surgery) and with expected stapled or handsewn intraperitoneal anastomosis. The exclusion criteria are mainly an emergent surgery; rectal cancer requiring total mesorectal excision and anastomosis expected below the peritoneal reflection; CRC requiring total or subtotal colectomy; CRC requiring transverse colectomy; recurrent CRC and locally advanced colorectal cancer requiring multi-visceral excision.

The 26 participating centres are equipped with a scope with near-infrared (NIR) light source allowing real-time ICG perfusion assessment. The co-investigators are experienced digestive surgeons trained to work with and without IOFA. They have considerable experience in working together on research projects and have a proven track-record of efficacy. Moreover, this study will receive valuable support from the Surgery Research Network (FRENCH) and the Surgical Research on Rectal Cancer Group (GRECCAR), which have proved their ability to recruit patients into various multicentric studies and with which the FLUOCOL-1 project has been discussed.

The duration of participation for each patient is 90 days. The 3 study visits are superimposed to the schedule of standard of care (V1: pre-operation visit of selection and inclusion; Surgery; V2: 30-day post-operation visit and V3: 90-day post-operation visit).

The surgeon will do the 1:1 randomization between V1 and the day before surgery (D-30 to D-1). To reduce the risk of bias, patients will be blinded to the study group and the randomization will be stratified on participating centres, Body Mass Index (BMI), physical status classification score (=ASA score), preoperative treatment and tumor location. Patient will be assigned in the intervention (IOFA) or the control group (no IOFA).

At the exception of the information given on the study to the patient, the gathering of the written consent, the randomization and the HRQoL questionnaires, the patient will be treated following standard of care. Study data are the data systematically collected in the patient medical file except for the HRQoL questionnaires that will be collected under the supervision of a research technician financed by the study. The technician will capture the study data and the de-identified pdf version of the medical reports (consultations and hospitalizations) in the electronic Case Report Form (eCRF) after every visit.

A total of 1010 patients will be necessary (39 patients in each centre during 36 months). An interim analysis for efficacy and futility is scheduled when half of the participants will have been recruited.

The ICG will be graciously provided by the manufacturer (SERB). An investigator meeting will be organized twice a year during the annual GRECCAR and FRENCH meetings. Newsletters will be sent every 3 months.

In case of positive results favoring IOFA, this study would define the use of IOFA as a standard of care in colorectal surgery. At the patient level, a significantly lower rate of AL will reduce hospital stay and stoma rate, and will ensure improved postoperative recovery, faster return to normal activity and better long-term oncologic outcomes. ;

Related Conditions & MeSH terms

• Anastomotic Leak
• Colorectal Cancer

• NCT number: NCT05168839
• Study type: Interventional
• Source: Centre Hospitalier Universitaire de Besancon
• Contact: Zaher Lakkis, MD, PhD
• Phone: +33.3.81.66.83.41
• Email: zlakkis@chu-besancon.fr
• Status: Recruiting
• Phase: Phase 3
• Start date: September 26, 2022
• Completion date: October 31, 2025