Minimal endoscopic sphincterotomy with papillary balloon dilation versus endoscopic sphincterotomy for the treatment of common bile duct stones (MARBLE Trial): study protocol for a multicenter randomized controlled trial.

Abstract

Background: The first-line treatment for common bile duct stones (CBDS) is endoscopic transpapillary stone removal, typically performed using either endoscopic sphincterotomy (EST) or endoscopic papillary balloon dilation (EPBD). However, EST is associated with risks of bleeding and perforation, while EPBD carries a significant risk of post-procedural pancreatitis. Recently, a combined approach involving minimal EST followed by EPBD (ESBD) has been reported to mitigate these drawbacks, offering potentially safer and more effective outcomes. Nevertheless, no prospective study has adequately evaluated the utility of ESBD, as prior studies were mainly observational or limited by small sample sizes. Therefore, we designed a randomized controlled trial to investigate whether ESBD is superior to EST for the treatment of small CBDS.

Methods: This study is a multicenter, randomized, open-label, parallel-group trial; outcome assessors will not be blinded, but objective predefined criteria will be used to minimize bias. Eligible participants will include patients aged 18 years or older diagnosed with CBDS who require endoscopic stone removal, with eligibility confirmed via imaging modalities. After confirming eligibility, patients will be randomly assigned in a 1:1 ratio to either the ESBD group or the EST group. In the ESBD group, a minimal sphincterotomy will first be performed, followed by balloon dilation for stone extraction. In the EST group, a medium incision extending beyond the hooding fold will be performed prior to stone extraction. The primary endpoint is the incidence of procedure-related adverse events, including pancreatitis, bleeding, and perforation. Secondary endpoints include technical success rate, clinical success rate, procedure time, need for lithotripsy, and stone recurrence rate.

Discussion: This study is the first multicenter, randomized controlled trial to prospectively evaluate the efficacy and safety of ESBD for the treatment of small CBDS. The findings are expected to determine whether ESBD can serve as a new standard therapeutic option compared with conventional EST.

Trial registration: Japan Registry of Clinical Trials: jRCT1040250008. Registered on 21 April 2025. ( https://jrct.mhlw.go.jp/en-latest-detail/jRCT1040250008 ).