Does omission of a loose seton before sphincter-preserving surgery achieve non-inferior fistula closure compared with routine loose seton placement in adults with single-tract cryptoglandular anal fistula in the Netherlands? Study protocol for the SETON multicentre randomised controlled non-inferiority trial and cost-utility analysis

Introduction Cryptoglandular anal fistulas are burdensome, often recurrent and frequently treated in two stages using a loose seton before definitive sphincter-preserving surgery. Although this practice is common, high-quality evidence supporting improved healing or functional outcomes is lacking. A trial is needed to determine whether omitting routine seton placement can reduce procedures, patient burden and costs without compromising fistula closure. Methods and analysis The SETON trial is a multicentre, randomised, unblinded non-inferiority trial with an integrated cost-utility analysis. Adults with a single-tract non-purulent mid-high or high cryptoglandular anal fistula will be randomised to loose seton placement for 8 weeks followed by definitive sphincter-preserving surgery, or to direct sphincter-preserving surgery without prior seton placement. The primary endpoint is fistula closure 26 weeks after final surgery, defined clinically and if needed confirmed by MRI or endoanal ultrasound. Secondary outcomes include recurrence, postoperative complications, pain, re-interventions, continence, fistula-related quality of life, generic health-related quality of life, return to work and cost-effectiveness. A sample size has been calculated for a non-inferiority design with fistula closure at 26 weeks as the primary endpoint. Assuming a conservative closure rate of 60% in the standard-care seton group, a one-sided alpha of 0.05, 80% power and a non-inferiority margin of 15 percentage points, 126 patients are required per group for analysis. Allowing for approximately 10% loss to follow-up, the total sample size will be 277 patients. Data will be analysed according to the intention-to-treat and per-protocol principle. Ethics and dissemination The protocol has been approved by the Medical Ethics Review Committee of the Amsterdam University Medical Center, location AMC (reference number: 2025.0826—NL-010338 R031541). Findings will be disseminated in peer-reviewed journals and presented at conferences, whether they are positive, negative or inconclusive. Trial registration number NL-010338