Clinical trial NCT05168839: Intraoperative Indocyanine Green Fluorescence Angiography in Colorectal Surgery to Prevent Anastomotic Leakage
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: Anastomotic leakage
Colorectal surgery
fluorescence angiography
Indocyanine green
Colic surgery
Complication
Prevention
Rectal surgery
Lead sponsor: Centre Hospitalier Universitaire de Besancon
Sponsor class: OTHER
First posted: 2021-12-23
Enrollment: 1010
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Anastomotic leakage 90 days after surgery
timeFrame: 90 days after surgery
Secondary outcomes:
measure: Change in planned anastomotic site.
timeFrame: During surgery
measure: Rate of patients with a defunctioning stoma.
timeFrame: Surgery time.
measure: Overall 30-day postoperative morbidity.
timeFrame: 30 days after surgery.
measure: Overall 90-day postoperative morbidity.
timeFrame: 90 days after surgery.
measure: Mortality rate.
timeFrame: 90 days after surgery.
measure: Hospital length of stay.
timeFrame: End of hospital stay.
measure: Postoperative reintervention.
timeFrame: 90 days after surgery.
measure: Quality of life assessment.
timeFrame: 90 days after surgery.
measure: Medico-economic analysis
timeFrame: 90 days after surgery.
Other outcomes:
Locations:
city: Amiens
country: France
facility: Centre Hospitalier Universitaire Amiens-Picardie
city: Annecy
country: France
facility: CH Annecy
city: Besançon
country: France
facility: Centre Hospitalier Universitaire de Besançon
city: Bourgoin-Jallieu
country: France
facility: Centre Hospitalier Bourgoin-Jallieu
city: Dijon
country: France
facility: University Hospital of Dijon
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: La Tronche
country: France
facility: Centre Hospitalier Universitaire de Grenoble
city: Lille
country: France
facility: Centre Hospitalier Universitaire de Lille
city: Lyon
country: France
facility: Centre lyonnais de chirurgie digestive
city: Lyon
country: France
facility: Centre Hospitalier Lyon-Sud
city: Marseille
country: France
facility: Hôpiatl Européen
city: Marseille
country: France
facility: Hôpital La Timone
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Marseille
country: France
facility: Hôpital Nord AP-HM
city: Marseille
country: France
facility: Hôpital St Joseph Marseille
city: Nancy
country: France
facility: CHU de Nancy
city: Paris
country: France
facility: Hôpital Saint Louis
city: Paris
country: France
facility: Hôpital Saint Antoine
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Hôpital Bicêtre
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Pontoise
country: France
facility: Centre Hospitalier de Pontoise
city: Reims
country: France
facility: Hôpital Robert Debré
city: Rennes
country: France
facility: Ch Pontchaillou
city: Rouen
country: France
facility: Centre Hospitalier Universitaire de Rouen
city: Saint-Herblain
country: France
facility: Santé Atlantique
city: Strasbourg
country: France
facility: Centre Hospitalier Universitaire de Strasbourg
city: Toulouse
country: France
facility: CHU de Toulouse
city: Toulouse
country: France
facility: Clinique TIVOLI
city: Tours
country: France
facility: Centre Hospitalier de Tours
city: vandoeuvre les Nancy
country: France
facility: Institut cancérologie de Lorraine
city: Villejuif
country: France
facility: Gustave Roussy
Study officials:
References:
citation: Wojcik M, Doussot A, Manfredelli S, Duclos C, Paquette B, Turco C, Heyd B, Lakkis Z. Intra-operative fluorescence angiography is reproducible and reduces the rate of anastomotic leak after colorectal resection for cancer: a prospective case-matched study. Colorectal Dis. 2020 Oct;22(10):1263-1270. doi: 10.1111/codi.15076. Epub 2020 May 18.