Post-procedural pancreatitis occurred significantly less often in patients who received rectal indomethacin following endoscopic retrograde cholangiopancreatography (ERCP), results of a large randomized trial showed.

A single post-ERCP dose of indomethacin was associated with a 45% reduction in the incidence of pancreatitis, including 50% fewer cases of moderate or severe pancreatitis.

The benefit was consistent across patient risk categories, although higher-risk patients tended to benefit more often, as reported in the April 12 New England Journal of Medicine.

“Our findings showed that one dose of rectal indomethacin given immediately after ERCP significantly reduced the incidence of post-ERCP pancreatitis in patients at elevated risk for this complication,” B. Joseph Elmunzer, MD, of the University of Michigan Medical Center in Ann Arbor, and colleagues wrote.

“Moreover, we found that prophylactic indomethacin decreased the severity of post-ERCP pancreatitis and was associated with a shorter hospital stay. In this trial, the number of high-risk ERCP patients who would need to be treated to prevent one episode of pancreatitis was 13.”

Post-ERCP pancreatitis adds an estimated $150 million annually to healthcare costs in the U.S. Studies of about three dozen drugs for post-ERCP prophylaxis have failed to demonstrate consistent efficacy, the authors noted in their introduction. Consequently, prophylaxis after ERCP is not widely practiced.

Preliminary trials of single-dose indomethacin and diclofenac after ERCP suggested efficacy for preventing pancreatitis, and a meta-analysis provided additional supporting evidence (Gut 2008; 57: 1262-1267). Nonetheless, the strategy has not come into widespread use, in part, because favorable results with other drugs subsequently have been disproved by additional investigation.

In addition, no studies have shown that nonsteroidal anti-inflammatory drugs (NSAIDs) provide incremental benefit over temporary pancreatic stents.

The unresolved status of NSAID prophylaxis after ERCP provided a rationale for a randomized, placebo-controlled trial to evaluate single-dose rectal indomethacin. Investigators at four U.S. centers prospectively enrolled patients who had an increased risk of post-ERCP pancreatitis. High risk was defined by the presence of one or more prespecified major criteria: suspicion of sphincter of Oddi dysfunction, history of post-ERCP pancreatitis, pancreatic sphincterotomy, precut sphincterotomy, more than eight cannulation attempts, pneumatic dilatation of an intact biliary sphincter, or ampullectomy. Patients also were eligible if they met certain minor criteria: women younger than 50, two or more prior episodes of pancreatitis, three or more injections of a contrast agent into the pancreatic duct, excessive injection of a contrast agent, or brush cytology involving the pancreatic duct. Eligible patients were randomized to receive two 50-mg indomethacin suppositories or two matching placebo suppositories immediately after ERCP. The primary outcome was post-ERCP pancreatitis, as defined in accordance with consensus criteria. The secondary outcome was development of moderate or severe post-ERCP pancreatitis. The final analysis included 602 patients, 82% of whom had clinically suspected sphincter of Oddi dysfunction. The indomethacin group had a 9.2% incidence of post-ERCP pancreatitis compared with 16.9% in the placebo group (P=0.005). The results translated into a number needed to treat (NNT) of 13. Moderate or severe pancreatitis occurred in 4.4% of the indomethacin arm and 8.8% of the placebo arm (P=0.03). The NNT for patients with a risk score of 1 was 21 (one major, two minor criteria), declining to 6 for patients with a risk score of 5 (four major, two minor inclusion criteria). Post-ERCP pancreatitis was associated with a significant increase in length of stay (4.0 versus 3.5 days, P<0.001). The risk of post-ERCP pancreatitis is influenced by operator experience and skill, as well as patient risk, commented David Bernstein, MD, of North Shore University Hospital in Manhasset, N.Y. The trial involved some of the most experienced ERCP operators in the U.S. Even so, the results are noteworthy. "This is an important finding and one that may change the standard of clinical practice in these patients at high risk of ERCP pancreatitis," Bernstein, who was not involved in the study, said in response to a request from MedPage Today. Primary source: New England Journal of Medicine Source reference: Elmunzer BJ, et al “A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis” N Engl J Med 2012; 366: 1414-1422.