Tranexamic acid to prevent anastomotic leak after rectal cancer surgery: protocol for a feasibility trial with embedded mechanistic analysis of the microbiome.

Abstract

Anastomotic leak is a major complication after anterior resection for rectal cancer, with reported rates of 10-15%. Recent evidence implicates the gut microbiome, where specific bacteria colonise the anastomotic site and secrete collagenase that weakens healing tissue. Preclinical studies demonstrate that tranexamic acid can inhibit this process when delivered rectally into the bowel lumen. This protocol outlines a feasibility trial of rectally administered tranexamic acid delivered via rectal catheter to the anastomotic site after anterior resection, accompanied by embedded microbiome and qualitative substudies. This is an open-label, single-centre, randomised controlled feasibility trial. 45 patients undergoing anterior resection for rectal or sigmoid cancer will be randomised 2:1 to receive tranexamic acid or sterile water, administered intraoperatively and on postoperative days 1-3 via a rectal catheter. Feasibility outcomes include assessment of recruitment, intervention adherence, protocol compliance and safety. Exploratory clinical outcomes include anastomotic leak and other postoperative complications. A mandatory microbiome substudy will characterise changes in microbial composition and bacterial collagenase activity, providing mechanistic insight into treatment response. An optional qualitative substudy will explore acceptability of the intervention from the perspectives of patients and healthcare professionals. The protocol was approved by the North West Liverpool Central Research Ethics Committee and the Medicines and Healthcare products Regulatory Agency on 30 October 2024 (24/NW/0254). Recruitment commenced on 7 January 2025 following receipt of site-specific approvals. Feasibility, mechanistic and qualitative findings will be disseminated through peer-reviewed publications, academic conferences and stakeholder engagement activities. The results will inform progression to a definitive phase III trial and shape key elements of study design. ISRCTN13727659.