Introduction
Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard for common bile duct stones (CBDS) clearance, but stone recurrence remains a significant clinical challenge, affecting 4%–24% of patients. Ursodeoxycholic acid (UDCA) is commonly used for prevention, but its efficacy is controversial, particularly for pigment stones, and its use is often limited by dose-dependent diarrhea. Peppermint oil, a hydrocholeretic agent with calcium-channel blocking properties, may offer an alternative by promoting biliary flushing and relaxing the sphincter of Oddi.
Aims & Methods
This prospective, randomized, open-label, active-controlled trial (NCT04484870) enrolled patients aged 18–80 years with complete CBDS clearance confirmed by ERCP. Participants were randomized (1:1) to receive Peppermint Oil (0.45 g, t.i.d., before meals) or UDCA (10 mg/kg/day, b.i.d.) for 6 months, with a 24-month follow-up. The primary endpoint was CBDS recurrence (defined as stones identified >6 months post-clearance). Recurrence-free survival was analyzed using Kaplan–Meier and Cox proportional hazards models. Outcome assessors were blinded to group allocation (PROBE design).
Results
A total of 211 patients (107 Peppermint Oil, 104 UDCA) were included in the ITT analysis. At 24 months, stone recurrence occurred in 25.2% (27/107) of the Peppermint Oil group and 37.5% (39/104) of the UDCA group (Log-rank P = 0.076). After adjusting for pre-specified variables (age, history of EST, CBD diameter, and periampullary diverticulum), Peppermint Oil showed a consistent trend towards risk reduction (adjusted HR = 0.69, 95% CI 0.41–1.14, P = 0.148). Periampullary diverticulum was identified as an independent risk factor for recurrence (HR = 1.76, 95% CI 1.02–3.03, P = 0.042). Liver function recovery trajectories were comparable between groups (P > 0.05). While overall adverse event rates were similar (13.1% vs. 8.7%, P = 0.417), the UDCA group had a significantly higher incidence of diarrhea (6.7% vs. 0%, P = 0.006). Menthol eructation (7.5%) and mild heartburn (4.7%) were more common with Peppermint Oil.
Conclusion
Peppermint oil (Danshu Capsule) demonstrated a favorable trend towards reducing CBDS recurrence compared to UDCA, although the primary endpoint did not reach statistical significance. Its distinct safety profile, particularly the absence of diarrhea, suggests it is a well-tolerated and promising alternative for long-term prevention, especially in patients who have undergone EST or are intolerant to UDCA.