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)
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Enrollment
- 1,010
- Locations
- 57
- Primary Endpoint
- Anastomotic leakage 90 days after surgery
Study Overview
Brief 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.
Detailed 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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Single (Participant)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adult patients (age >18 years)
- •Scheduled to undergo elective left colectomy or high rectal resection for cancer with intraperitoneal anastomosis.
- •Signed consent
- •Affiliated to the French social security system (CMU included).
Exclusion Criteria
- •Emergent surgery.
- •Rectal cancer requiring total mesorectal excision and anastomosis below the peritoneal reflexion.
- •Colon cancer requiring total or subtotal colectomy defined as a right colectomy extended to the splenic flexure or more).
- •Colon cancer requiring transverse colectomy.
- •Recurrent colorectal cancer.
- •Locally advanced colorectal cancer requiring multi-visceral excision.
- •History of colectomy.
- •Associated concomitant resection of other organ (liver, etc.).
- •Previous pelvic radiotherapy for pathology unrelated to diagnosis with colon cancer e.g. treatment for prostate cancer.
- •Inflammatory bowel disease.
- •History of known allergy to indocyanine.
- •Pregnant patients.
- •Refusal to participate or inability to provide informed consent.
- •Protected adults (individuals under guardianship by court order).
Arms & Interventions
FLUO+
Experimental arm = surgery with IOFA.
In the experimental arm, cancer resection and anastomosis will be performed after assessment of descending colon perfusion using intravenous injection of indocyanine green 0.1ml/kg.
Intervention: FLUO+ : Intraoperative fluorescence angiography (IOFA) with indocyanine green (ICG). (Drug)
FLUO-
Control arm = Surgery without IOFA.
In the control arm, cancer resection and anastomosis will be performed without intraoperative fluorescence angiography.
Outcomes
Primary Outcomes
Anastomotic leakage 90 days after surgery
Time Frame: 90 days after surgery
The primary outcome is the occurence of an anastomotic leakage during the 90 days following surgery. Anastomotic leakage is defined as any clinical signs of leakage diagnosed by radiological examination or surgical exploration, or as any isolated pelvic organ infection without leakage evidence, as defined by the International Rectal Cancer Study Group.
Secondary Outcomes
- Rate of patients with a defunctioning stoma.(Surgery time.)
- Hospital length of stay.(End of hospital stay.)
- Change in planned anastomotic site.(During surgery)
- Overall 30-day postoperative morbidity.(30 days after surgery.)
- Mortality rate.(90 days after surgery.)
- Medico-economic analysis(90 days after surgery.)
- Overall 90-day postoperative morbidity.(90 days after surgery.)
- Postoperative reintervention.(90 days after surgery.)
- Quality of life assessment.(90 days after surgery.)