Intracorporeal Versus Extracorporeal Anastomotic After Laparoscopic Right Colectomy

A Multicenter Randomized Clinical Trial Comparing Intracorporeal and Extracorporeal Ileocolic Anastomotic After Laparoscopic Right Colectomy for Colon Cancer (COLOR IV)

Background: Laparoscopic assisted right hemicolectomy is recommended for right colon cancer. As a more minimally invasive procedure, intracorporeal ileocolic anastomosis has potential advantages: reducing torsion and traction on the mesentery, reducing skin incision length and enhancing postoperative recovery. However, the longer operative time, greater risk of intra-abdominal infection and steep learning curve for intestinal anastomosis performed under laparoscopic conditions, does this increase the incidence of postoperative complications, especially the incidence of anastomotic leakage, and whether it affects There is no high-level research evidence on the survival of patients.

Study design: COlOR IV study is an international prospective, multicenter, randomized controlled clinical study of intraperitoneal anastomosis versus extraperitoneal anastomosis after laparoscopic right hemicolectomy for colon cancer . The study will include a quality assessment phase before randomisation to ensure required competency level and uniformity of the intracorporeal and extracoporeal techniques.

Endpoint: Primary outcome is anastomotic leakage within 30 days after surgery. Main secondary endpoint is 3-year disease-free survival rate. Secondary endpoints are mortality and morbidity, postoperative recovery, overall survival, surgical specimen quality, quality of life.

Statistics: The primary endpoint is anastomotic leakage within 30 days after surgery. The anastomotic leakage rate was set to 2% in the both groups, and an increase in the incidence of anastomotic leakage of 2.5% was considered inferior. The one-sided significance level was 0.025, the power was 0.9. The dropout rate was 20%, and taking into account the post-randomization analysis (dropout 5%), the total sample size was 1158. There were 579 cases in the intracorporeal anastomosis group and 579 cases in the extracorporeal anastomosis group.

Main selection: Patients with histologically proven right colon cancer (cecum, ascending colon and proximal 1/3 of the transverse colon malignant tumor), clinically stage I-III, and intention for right hemicolectomy with primary anastomosis.

Hypothesis: The hypothesis is that intracoporeal anastomosis will have comparable anastomotic leak rate and 3-year DFS, but faster postoperative recovery with extracoporeal anastomosis.

Study Overview

• Status: Not yet recruiting
• Conditions: Colon Cancer
• Intervention / Treatment: Procedure: Intracorporeal anastomotic after LRC; Procedure: Extracorporeal anastomotic after LRC

• Study Type: Interventional
• Enrollment (Estimated): 1158
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hongwei Yao, Prof; Phone Number: +8613611015609; Email: yaohongwei@ccmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

1. Age: 18 ~ 80 years, male or female;
2. Histological or cytological diagnosis of right colon cancer (cecum, ascending colon and proximal 1/3 of the transverse colon cancer);
3. Stage I-III according to the AJCC-TNM classification including downstaged tumor based on adequate imaging of the thorax and abdomen;
4. Intention for right hemicolectomy (including extended right hemicolectomy) with primary anastomosis;
5. Informed consent according to local requirements Exclusion criteria

1) T4b tumor determined by CT scan; 2) Malignancy other than adenocarcinoma at histological examination ; 3)Other malignancies in medical history, except adequately treated basocellular carcinoma of the skin or in situ carcinoma of the cervix uteri; 4) Previous history of colorectal cancer or synchronous multiple colorectal malignancies; 5) Complications requiring emergency surgery (obstruction, perforation, etc); 6) Planned synchronous abdominal organ resections; 7) Pregnant or lactating women; 8) Familial Adenomatosis Polyposis Coli (FAP), active Crohn's disease or active ulcerative colitis; 9) Absolute contraindication to general anesthesia or laparoscopic surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intracorporeal anastomotic after LRC	Procedure: Intracorporeal anastomotic after LRC; Complete laparoscopic dissection of the mesocolon is mandatory. D2 or D3/CME is optional. And the extent of colon resection is based on the location of the tumor while the ileocecal resection is excluded. After fully mobilization of the colon and mesentery, the terminal ileum and transverse colon will be transected by a laparoscopic linear stapler. The side-to-side anastomosis is performed laparoscopically. The enterotomy is closed by a double-layer suture. All the anastomotic procedures are completed laparoscopically. The specimen is then removed through a Pfannenstiel incision within a specimen bag.
Active Comparator: Extracorporeal anastomotic after LRC	Procedure: Extracorporeal anastomotic after LRC; The procedures of the mobilization and vessel ligation are similar. After that, the mobilized colon and terminal ileum are brought out through the upper mid-line incision with the wound protector. The colon and terminal ileum are similarly dissected distally to the specimen with a stapling device. The side-to-side anastomosis is completed and the anastomotic site is reinforced. The anastomotic bowel is returned to the abdominal cavity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anastomotic leak	Anastomotic leakage is defined as a defect of the intestinal wall at the anastomotic site leading to a communication between intra- and extraluminal compartments. Diagnosis of anastomotic leakage: The radiological examination (CT abdomen) will be completed if clinically suspected AL. AL is confirmed clinically, radiologically, endoscopically or intraoperatively. The severity of anastomotic leakage was judged with reference to the Clavien-Dindo classification.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality		5 years
Disease-free survival rate	Main secondary outcome	3/5 years
Overall survival		3/5 years
morbidity		5 years
Duration of surgery	from incision to suture completion	Intraoperative
Duration of anastomosis	from the start of dissection of the bowel to the compeletion of the anastomosis	Intraoperative
Surgical incision length		Intraoperative
Conversion rate	conversion to open surgery or conversion to extracorporeal anastomosis	1 month
Pain score (VAS score)	The Visual Analogue Scale (VAS) measures pain intensity. The VAS consists of a 10cm line, with two end points representing 0 ('no pain') and 10 ('pain as bad as it could possibly be'). Ask the patient to rate their current level of pain by placing a mark on the line.	1-3 days
Time to first flatus passage after surgery	The day of surgery is day 0. The time interval between the day of the first flatus passage after surgery and the day of surgery.	1 month
Time to first stool passage after surgery	The day of surgery is day 0. The time interval between the day of the first stool passage after surgery and the day of surgery.	up to 1 week
Time to first oral intake	The day of surgery is day 0. The time interval between the day of the first oral intake after surgery and the day of surgery.	up to 1 week
Length of hospital stay after surgery	days from surgery to discharge	1 month
Specimen quality	West pathological assessment criteria. Grading of the plane of mesocolic dissection.; Muscularis propria plane：little bulk to mesocolon with disruptions extending down onto the muscularis propriapropria; Intramesocolic plane: moderate bulk to mesocolon with irregularity but the incisions do not reach down to the muscularis propria; Mesocolic plane: intact mesocolon with a smooth peritoneal-lined surface	1 month
Health-related quality of life	EORTC QLQ-CR29 and C30: questionnaires to evaluate the overall quality of life of patients with colorectal cancer, including 30 and 29 items, respectively, to score patients' overall quality of life, function, and symptoms. These are coded with four-point scales, namely "Not at all", "A little", "Quite a bit" and "Very much."	1 year
health-related quality of life	EQ 5D-5L (Euroqol): This questionnaire is a simple, generic tool for describing and assessing health-related quality of life. It consists of 5 items (mobility, personal care, activities of daily living, pain and anxiety and depression) that answer questions on a 5-point scale ranging from "no problem" (level 1) to "very severe" (level 5).	1 year
Incision herniation	The incision herniation is classified by the criteria of the European Hernia Society. The location (Midline/Lateral) and size (length and width) of the herniation will be recorded.	1 year

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital
• Investigators: Principal Investigator: Zhongtao Zhang, Prof, Department of General Surgery, Beijing Friendship Hospital, Capital Medical University; Principal Investigator: Hendrik J Bonjer, Prof, Amsterdam UMC, location VUmc; Study Director: Hongwei Yao, Prof, Department of General Surgery, Beijing Friendship Hospital, Capital Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: May 23, 2022
• First Submitted That Met QC Criteria: August 7, 2022
• First Posted (Actual): August 9, 2022

Study Record Updates

• Last Update Posted (Estimated): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: anastomotic leak; laparoscopic; intracorporeal anastomosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms
• Other Study ID Numbers: COLOR IV Trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We are not sharing confidential individual patient data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No