Comparison of SIS-reinforced anastomosis and conventional anastomosis on postoperative AL for middle and low rectal cancer: a study protocol for multicenter randomized controlled clinical trial

Postoperative anastomotic leak (AL) remains a major complication after radical resection of middle and low rectal cancer. Current preventive strategies, such as the creation of a diverting ostomy, effectively mitigate clinical complications. However, they are associated with considerable patient burdens. This clinical trial aims to evaluate whether SIS-reinforced anastomosis with small intestinal submucosa (SIS) can reduce the incidence and severity of AL. This trial was designed as a prospective, parallel, superiority, randomized controlled trial (RCT), involving 44 centers, to compare conventional anastomosis (control group) versus SIS-reinforced anastomosis (experimental group) in radical resection for middle and low rectal cancer. Participants will be randomized 1:1 with stratified block randomization. The primary endpoint is the incidence of AL within 30 days postoperatively to assess the efficacy of SIS-reinforced anastomosis. The secondary endpoints are the severity of AL graded according to the ISREC classification within 30 days postoperatively, incidence of preventive ostomy, reoperation, nosocomial infection, anastomotic stenosis, delayed AL, and the incidence of postoperative diverting ostomy. Furthermore, each participant will be followed for 1 year, and baseline data and safety data will be collected simultaneously. We hypothesized that the incidence of AL within 30 days postoperatively would be 5% and 10% in the experimental group and control group, respectively. With a two-sided α of 0.05 and a power of 0.8, the sample size was calculated to be 966 participants (483 per group), considering a 10% dropout rate. SIS-reinforced anastomosis is expected to reduce the incidence and severity of AL and related mortality after radical resection of middle and low rectal cancer. Moreover, SIS-reinforced anastomosis is expected to potentially reduce unnecessary preventive ostomy. ClinicalTrials.gov NCT07209787. Registered on October 7, 2025, https://clinicaltrials.gov/search?term=NCT07209787&viewType=Card .