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PHILADELPHIA -- Use of a higher-dose regimen of rectal indomethacin did not confer any additional benefit over the standard dose in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) who were at high risk of post-procedure pancreatitis, an investigator reported here.

Among patients who received 200 mg of rectal indomethacin directly after ERCP, the incidence of pancreatitis was 12.5% compared with 14.8% among those who were given the standard 100-mg dose, which was not a statistically significant difference, according to Evan L. Fogel, MD, of Indiana University in Indianapolis.

And the incidence of moderate-to-severe pancreatitis was identical in the two groups, at 5.4%, he said during a presidential plenary session at the .

Pancreatitis is the most frequent complication of ERCP, a procedure used to treat problems of the bile and pancreatic ducts. Historically, the rate of this complication has reached as high as 20% in high-risk patients.

"Nonsteroidal anti-inflammatory drugs are attractive for the pharmacologic prevention of pancreatitis because they are widely available, inexpensive, and easily administered. They also have a favorable risk profile when given as a one-time dose in appropriately selected patients," Fogel said.

published in 2012 demonstrated that the use of rectal indomethacin in doses of 100 mg reduced the rates of pancreatitis to 9.2% compared with 16.9% with placebo (P=0.005). That study showed that indomethacin was "unequivocally effective" for preventing post-ERCP pancreatitis, and the drug is now the standard of care for high-risk patients, he said.

"Unfortunately, pancreatitis risks do remain unacceptably high in these patients, despite the use of indomethacin and prophylactic pancreatic stent placement," he said.

The maximum daily dose of indomethacin is 200 mg, and the half-life of the drug is 4.5 hours. Fogel and his colleagues hypothesized that a larger initial dose, followed by a second dose 4 hours later, might have more sustained effects.

Therefore, the team conducted a prospective trial from 2013 to 2018 at six U.S. tertiary care centers, including 1,037 patients who were randomized to receive 150 mg of indomethacin following the ERCP plus an additional 50 mg after 4 hours, or the standard 100 mg dose plus placebo.

In addition to similar rates of post-procedure pancreatitis, the high-dose and standard-dose groups did not differ in rates of other complications (P>0.05 for all):

• Bleeding, 1.5% versus 1.2%
• Perforation, 0.8% versus 0.8%
• Infection, 1.9% versus 2.3%
• Renal failure, 0.6% versus 0%
• Cardiac events, 0% versus 0.2%
• Cerebrovascular events, 0.2% versus 0%

There were no deaths at 30-day follow-up, Fogel reported.

There were two subgroups who potentially benefited: "Let me remind you that this is a preliminary analysis, and the fine statistical points are still being worked out," but it appeared that patients who had a history of post-ERCP pancreatitis and those with pancreatic acinarization may have had some benefit with the 200 mg treatment, he said.

The dose escalation did not appear to confer an advantage over the standard dose, he concluded. "Additional interventions -- drugs, devices, and techniques -- are needed to further reduce the risk of post-ERCP pancreatitis."

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