Low-dose rectal indomethacin to prevent post-ERCP pancreatitis: results of a large Chinese multicenter randomized noninferiority trial

Abstract Routine rectal administration of indomethacin before endoscopic retrograde cholangiopancreatography (ERCP) is recommended for prevention of post-ERCP pancreatitis (PEP). Preliminary evidence suggests that the use of 100 mg of indomethacin can reduce the PEP rate; however, the efficacy of a lower dose for PEP prevention remains uncertain. In this randomized, single-blind, noninferiority trial conducted at four centers in China, patients (aged ≥18 years) who were scheduled to undergo ERCP and had a serum amylase level within the normal range were randomly assigned (1:1) to receive 50 mg or 100 mg rectal indomethacin before ERCP. The primary outcome was the PEP rate. Between September 11 2021 and July 1 2024, 2770 patients were enrolled, with 2562 included for intention-to-treat analysis. PEP occurred in 100 (7.7%) of the 1293 patients in the regular-dose group and 103 (8.1%) of the 1269 patients in the low-dose group (risk difference 0.38%; 95%CI –1.71 to 2.47; P = 0.72 for noninferiority). For prevention of PEP, 50 mg of indomethacin was noninferior to 100 mg. The prophylactic use of 50 mg of indomethacin can therefore be considered for PEP prevention in the Chinese population. In addition, for people who have a history of pancreatitis, 100 mg of rectal indomethacin may be preferable for prevention of PEP.