Safety and Effectiveness of the Colovac Anastomosis Protection Device Compared with Diverting Ileostomy after Low Anterior Resection: Protocol for an International, Multicentre, Prospective, Non-Randomised Comparative Study (SAFE-3)

INTRODUCTION:Diverting loop ileostomy (DLI) after low anterior resection for rectal cancer reduces the clinical consequences of anastomotic leakage but is associated with significant morbidity, impaired quality of life and the need for a second operation for stoma closure. Temporary intraluminal bypass devices have been developed to protect the anastomosis while avoiding DLI. However, high-quality prospective data comparing such devices with standard DLI remain limited. This study aims to evaluate the safety and effectiveness of the Colovac device compared with DLI. METHODS AND ANALYSIS:SafeHeal Studies (SAFE-3), consisting of SafeHeal Standard of Care (Diverting Ileostomy) study (SH-SOC23) and SafeHeal Colovac Anastomosis Protection Device Evaluation Pivotal Study (SAFE-3CV), is an international, multicentre, prospective, non-randomised comparative study comprising two sequential cohorts: SH-SOC23 (standard-of-care diverting ileostomy control) and SAFE-3CV (Colovac anastomosis protection device). A total of 233 patients will be enrolled (SAFE-3CV n=108-120; SH-SOC23 n=132) across 25 centres in 4 countries. The primary endpoints are the rate of major complications at 9 months for safety and stoma avoidance at day 10 for effectiveness. Secondary outcomes include overall postoperative morbidity, stoma-related complications, reoperation rates, length of stay and stoma avoidance. Sample size calculation is based on non-inferiority assumptions. Data will be analysed using intention-to-treat principles, with propensity score adjustment to account for baseline differences between cohorts. Comparative analyses will include logistic regression and sensitivity analyses. ETHICS AND DISSEMINATION:The study was approved by ethics committees at the country level or at individual sites as per individual country requirements. An independent safety monitoring committee regularly reviews adverse events and safety data throughout the study. Results will be disseminated through peer-reviewed publications and presentations at international meetings. TRIAL REGISTRATION NUMBERS:SH-SOC23: NCT06152276 and SAFE-3CV: NCT07116668.