PHILADELPHIA — Rectal indomethacin dose escalation in high-risk patients undergoing endoscopic retrograde cholangiopancreatography did not confer any benefit over the standard dose for the prevention of post-ERCP pancreatitis, according to study results presented at the American College of Gastroenterology Annual Meeting.
“Pancreatitis is the most frequent complication of ERCP, with post-ERCP pancreatitis [PEP] rates historically as high as 20% in high-risk patients,” Evan L. Fogel, MD, MSc, a professor of medicine at Indiana University School of Medicine, said during his presentation. “NSAIDS are attractive in the pharmacologic prevention of PEP because they are widely available, inexpensive and easily administered.”
Fogel noted that since data were published in The New England Journal of Medicine demonstrating that rectal indomethacin significantly reduced the incidence of post-ERCP pancreatitis in patients at high risk for the condition, indomethacin has become the standard of care for the prevention of PEP.
Currently, the recommended maximum daily dose of indomethacin is 200 mg in divided doses, Fogel said. However, as Fogel noted, the half-life is only approximately 4.5 hours.
As a result, Fogel and colleagues hypothesized that a higher initial dose of indomethacin followed by a second dose might further lower PEP rates in high-risk patients, and then lead to a more sustained effect.
The researchers conducted a prospective, randomized, double-blind trial from July 2013 to March 2018 across six U.S. tertiary referral centers to assess their hypothesis.
Inclusion criteria included patients aged under 50 years and female sex, as well as a history of recurrent pancreatitis, which was defined as two or more episodes.
Patients were excluded if they were aged under 18 years, pregnant or breastfeeding, unwilling to consent or follow protocol, or had factors that protected against PEP.
Patients either received 150 mg of indomethacin immediately post-ERCP and 50 mg of indomethacin 4 hours post-ERCP (n = 522; 80.7% female), or 100 mg of indomethacin plus placebo immediately post-ERCP and placebo 4 hours post-ERCP (n = 515; 76.1% female).
PEP occurred in 14.8% of patients who received 100 mg of indomethacin, and 12.6% of patients who received 200 mg of indomethacin (P < .05), which, as Fogel noted, was not significantly different.
The difference between the two groups regarding adverse events was quite similar.
Six patients who received 100 mg of indomethacin reported a gastrointestinal hemorrhage compared with eight patients who received 200 mg.
Additionally, zero patients who received 100 mg, and three patients who received 200 mg, reported renal failure.
No allergic reactions or death at 30-day follow-up were observed.
“Dose escalation to 200 mg of rectal indomethacin does not appear to confer an advantage over the standard 100 mg regimen,” Fogel said. “Additional interventions ... are necessary to further reduce the risk of post-ERCP pancreatitis.” – by Ryan McDonald
Fogel EL, et al. Abstract 1. Presented at: American College of Gastroenterology Annual Scientific Meeting; Oct. 5-10, 2018; Philadelphia.
Disclosures: The researchers report no relevant financial disclosures.