Rectal indomethacin did not prevent post-endoscopic retrograde cholangiopancreatography pancreatitis in a randomized controlled trial.
Since the publication of a randomized controlled trial in 2012 that found rectal indomethacin significantly reduced the risk for post-ERCP pancreatitis (PEP) in high risk patients, this NSAID has been used extensively, and the European Society for Gastrointestinal Endoscopic recommended routine rectal indomethacin or diclofenac during ERCP in 2014. “However, despite these recommendations, the use of rectal NSAIDs in patients not considered to be at high-risk for PEP (the average-risk patient) is unproven,” the researchers wrote.
Therefore, they performed a prospective, randomized, double blind, placebo-controlled trial of 449 consecutive patients who underwent ERCP at Dartmouth Hitchcock Medical Center from March 2013 through December 2014. They randomly assigned 223 patients to receive two 50-mg indomethacin suppositories and 226 patients to receive two inert placebo suppositories during the procedure. Baseline clinical and procedural characteristics were comparable between groups, and about 70% of patients were at average risk for PEP.
Whether rectal indomethacin reduced the rate of PEP vs. placebo served as the primary outcome, with PEP defined as new-onset upper-abdominal pain, an increased lipase level greater than three times the upper limit of normal, and hospitalization after ERCP for at least 2 consecutive nights. Severity of PEP in the indomethacin vs. placebo group served as the secondary outcome.
The study was terminated due to futility. PEP occurred in 7.2% of the indomethacin group vs. 4.9% of the placebo group (P = .33). Severe or moderately severe PEP each occurred in one patient in the placebo group vs. none in the indomethacin group (P = 1). Rates of GI bleeding, death or 30-day hospital readmission were comparable between groups.
“Prophylactic rectal indomethacin did not reduce the incidence or severity of PEP in consecutive patients undergoing ERCP,” the researchers concluded. “Guidelines that recommend the administration of rectal indomethacin in all patients undergoing ERCP should be reconsidered.”
“Despite a decades long search for the ‘holy grail’ of an inexpensive, nontoxic agent to prevent PEP, only rectal NSAIDs seem to have emerged as feasible, and until the present study, moderately effective. The current evidence provided by Levenick et al throws some water on that fire,” Martin L. Freeman, MD, of the division of gastroenterology, hepatology and nutrition at University of Minnesota, and Richard A. Kozarek, MD, of the Digestive Disease Institute at Virginia Mason Medical Center in Seattle, wrote in a related editorial. They recommended that endoscopists “continue to administer rectal NSAIDs for high-risk patients, but realize that they are unlikely to be the panacea that has been suggested.” – by Adam Leitenberger
Disclosure: The researchers and editorial authors report no relevant financial disclosures.