Rectal diclofenac versus indomethacin for prevention of post-ERCP pancreatitis 

Kang X et al, Gut. 2025;74(7):1094-1102
Pre-procedure application of 100 mg rectal diclofenac was not superior to the same dose of indomethacin regarding prevention of post-ERCP pancreatitis in a randomized multicenter study involving 1204 patients.

Background: Recent meta-analyses suggested diclofenac may be superior to indomethacin in preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). The aim of our study was to compare the efficacy of 100 mg rectal indomethacin versus diclofenac on PEP incidences. Design: This multicentre, double-blinded, randomised controlled trial was conducted in nine tertiary centres in China. Patients with low and high risk for PEP and native papilla were randomly allocated (1:1) to receive 100 mg diclofenac or 100 mg indomethacin rectally before ERCP. The primary outcome was the occurrence of PEP defined by the Cotton consensus. The intention-to-treat principle was conducted for the analysis. Results: The trial was terminated early for futility after the predetermined first interim analysis. Between June 2023 and May 2024, 1204 patients were randomised into the diclofenac group (n = 600) or indomethacin group (n = 604). Baseline characteristics were balanced. The primary outcome occurred in 53 patients (8.8%) of 600 patients allocated to the diclofenac group and 37 patients (6.1%) of 604 patients allocated to the indomethacin group (relative risk = 1.44; 95% confidence interval [CI]: 0.96–2.16, p = 0.074). PEP occurred in 35 (14.2%) of 247 high-risk patients in the diclofenac group and 26 (9.8%) of 266 high-risk patients in the indomethacin group (p = 0.124). PEP incidences were also comparable in low-risk patients between the 2 groups (18/353 (5.1%) vs. 11/338 (3.3%), p = 0.227). Other ERCP-related complications did not differ between the 2 groups.

Conclusion: Pre-procedure 100 mg rectal diclofenac was not superior to the same dose of rectal indomethacin regarding preventing post-ERCP pancreatitis (PEP). These findings supported current clinical practice guidelines of 100 mg indomethacin or diclofenac for PEP prophylaxis in patients without contraindications.