INDOMETHACIN WITH OR WITHOUT PROPHYLACTIC PANCREATIC STENT TO PREVENT PANCREATITIS AFTER ERCP

Background: The combination of rectally administered indomethacin and placement of a prophylactic pancreatic stent is recommended to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients. Preliminary evidence suggests that the use of indomethacin may eliminate or substantially reduce the need for stent placement, a technically complex, costly, and potentially harmful intervention.

Methods: In this multicenter, randomized, non-inferiority trial, patients at high risk for post-ERCP pancreatitis were randomly assigned to receive rectal indomethacin alone or the combination of indomethacin plus a prophylactic pancreatic stent. Patients, treating clinicians, and outcomes assessors were blinded to study group assignment. To declare non-inferiority, the upper bound of the two-sided 95% confidence interval for the difference in post-ERCP pancreatitis (indomethacin alone – indomethacin plus stent) would have to be less than 5% (non-inferiority margin).

Findings: A total of 1950 patients were randomized. Post-ERCP pancreatitis occurred in 145 of 975 patients (14.9%) in the indomethacin alone group and in 110 of 975 (11.3%) in the indomethacin plus stent group (risk difference 3.6%; 95% confidence interval, 0.6%-6.6%; p=0.18 for non-inferiority). A post hoc intention-to-treat analysis of the risk difference between groups showed that indomethacin alone was inferior to the combination of indomethacin plus prophylactic stent (p=0.01). The relative benefit of stent placement was generally consistent across study subgroups but appeared more prominent among patients at highest risk for pancreatitis.

Conclusion: For preventing post-ERCP pancreatitis in high-risk patients, a strategy of indomethacin alone was not as effective as a strategy of indomethacin plus prophylactic pancreatic stent placement.

Funding: National Institutes of Health grant U01DK104833.