A double-blind, randomized, placebo-controlled trial found that rectal indometacin was safe and effective at reducing the incidence of postextracorporeal shock wave lithotripsy (ESWL) pancreatitis. These findings were published in The Lancet Gastroenterology and Hepatology.

The Rectal Indometacin to Prevent post-ESWL Pancreatitis (PIREP) trial was conducted at the Changhai Hospital in China from 2016 to 2019. Patients (N=1370) admitted with chronic pancreatitis undergoing ESWL for pancreatic stones were randomly assigned to receive 100 mg indometacin suppository (n=685) or glycerin suppository (n=685) within 30 minutes of the procedure. Patients were assessed for post-ESWL complications and pancreatitis during the first 24-hours.

The indometacin and control cohorts were aged mean 46 (SD, 35-54) and 47 (SD, 37-54) years at enrollment, 72% and 71% were men, mean body mass index was 21.40 (SD, 3.01) and 21.46 (SD, 3.14) kg/m2, 65% and 64% had idiopathic pancreatitis, and patients underwent 1.97 (SD, 0.97) and 1.95 (SD, 0.92) ESWL sessions, respectively.

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Post-ESWL complications were observed among 9% of the indometacin and 14% of the control cohorts (relative risk [RR], 0.66; 95% CI, 0.49-0.88; P =.0059). Post-ESWL pancreatitis occurred among fewer indometacin recipients (9% vs 12%; RR, 0.71; 95% CI, 0.52-0.98; P =.042). Fewer than 1% of post-ESWL pancreatitis events were moderate and no incidence was severe.

Among the intervention and control cohorts, transient adverse events of asymptomatic hyperamylasemia (28% vs 29%; P =.67), hematuria (3% vs 4%; P =.35), hematemesis (1% vs 2%; P =.40), melena (3% vs 2%; P =.73), and overall events (34% vs 37%; P =.37) did not differ between groups, respectively.

In subgroup analyses, indometacin was preferred among women (RR, 0.51; 95% CI, 0.29-0.90; P =.020), patients with idiopathic pancreatitis (RR, 0.62; 95% CI, 0.42-0.93; P =.020), and those without steatorrhea (RR, 0.66; 95% CI, 0.47-0.93; P =.016). With the exception of patients who had hereditary or familial pancreatitis, all other subgroups tended to favor indometacin.

This study may be limited by the imbalance in etiologies of pancreatitis.

These data indicate that preprocedural rectal indometacin was safe and effective at reducing post-ESWL pancreatitis among patients with chronic pancreatitis undergoing ESWL for pancreatic stones.


Qian Y-Y, Ru N, Chen H, et al. Rectal indometacin to prevent pancreatitis after extracorporeal shock wave lithotripsy (RIPEP): a single-centre, double-blind, randomised, placebo-controlled trial. Lancet Gastroenterol Hepatol. 2022;7(3):238-244. doi:10.1016/S2468-1253(21)00434-9