Correction to: Rectal indomethacin alone versus indomethacin and prophylactic pancreatic stent placement for preventing pancreatitis after ERCP: study protocol for a randomized controlled trial.

An amendment to this paper has been published and can be accessed via the original article.

Rectal indomethacin alone versus indomethacin and prophylactic pancreatic stent placement for preventing pancreatitis after ERCP: study protocol for a randomized controlled trial.

BACKGROUND: The combination of prophylactic pancreatic stent placement (PSP) - a temporary plastic stent placed in the pancreatic duct - and rectal non-steroidal anti-inflammatory drugs (NSAIDs) is recommended for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. Preliminary data, however, suggest that PSP may be unnecessary if rectal NSAIDs are administered. Given the costs and potential risks of PSP, we aim to determine whether rectal indomethacin obviates the need for pancreatic stent placement in patients undergoing high-risk ERCP. METHODS/DESIGN: The SVI (Stent vs. Indomethacin) trial is a comparative effectiveness, multicenter, randomized, double-blind, non-inferiority study of rectal indomethacin alone versus the combination of rectal indomethacin and PSP for preventing PEP in high-risk cases. One thousand four hundred and thirty subjects undergoing high-risk ERCP, in whom PSP is planned solely for PEP prevention, will be randomized to indomethacin alone or combination therapy. Those who are aware of study group assignment, including the endoscopist, will not be involved in the post-procedure care of the patient for at least 48 hours. Subjects will be assessed for PEP and its severity by a panel of independent and blinded adjudicators. Indomethacin alone will be declared non-inferior to combination therapy if the two-sided 95 % upper confidence bound of the treatment difference is less than 5 % between the two groups. Biological specimens will be obtained from trial participants and centrally banked. DISCUSSION: The SVI trial is designed to determine whether PSP remains necessary in the era of NSAIDs pharmacoprevention. The associated bio-repository will establish the groundwork for important scientific breakthrough. TRIAL REGISTRATION: NCT02476279, registered June 2015.

Incidence and predictors of post-ERCP pancreatitis in patients with suspected sphincter of Oddi dysfunction undergoing biliary or dual sphincterotomy: results from the EPISOD prospective multicenter randomized sham-controlled study.

BACKGROUND AND STUDY AIM: Pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) is a significant and potentially life-threatening adverse event and is common in patients with suspected sphincter of Oddi dysfunction (SOD). Here we aimed to identify predictors of the risk in this population. PATIENTS AND METHODS: The Evaluating Predictors and Interventions in SOD (EPISOD) study prospectively enrolled 214 post-cholecystectomy patients with SOD type III in seven US centers. Patients were randomized, using a 2:1 allocation, to sphincterotomy or sham procedure, irrespective of the results of sphincter of Oddi manometry. Patients in the sphincterotomy arm who had elevated pancreatic sphincter pressure were randomized to biliary only or to dual (biliary and pancreatic) sphincterotomy. All but one patient received prophylactic pancreatic stents, but none received pharmacological prophylaxis. Post ERCP pancreatitis (PEP) was defined as acute pancreatitis within the subsequent 7 days. Blinded research coordinators at each site called patients at 1 week post-procedure. RESULTS: PEP occurred in 26 patients, in 10.6 % (15/141) in the sphincterotomy arm and 15.1 % (11/73) in the sham arm; unadjusted relative risk 0.71 (95 % confidence interval [95 %CI] 0.34 - 1.46). PEP rate was not significantly different in patients who received sphincterotomy compared with those undergoing sham treatment. In addition, the proportion was not statistically different in those who received biliary sphincterotomy alone (12/94; 12.8 % [95 %CI 6.0 % - 19.5 %]) compared with dual sphincterotomy (3/47; 6.4 % [95 %CI 0.0 % - 13.4 %]). Multivariate analysis identified an interaction between duration of ERCP and sedation type (P < 0.02). CONCLUSION: The performance of biliary or dual sphincterotomy does not increase the risk of PEP in patients suspected of SOD. However, the high rate of PEP in patients with suspected SOD, despite pancreatic stenting in expert centers, is confirmed in this prospective study. The combined effect of duration of ERCP and sedation type on the development of PEP should be further explored.Clinicaltrials.gov registration: NCT00688662.

Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial.

IMPORTANCE: Abdominal pain after cholecystectomy is common and may be attributed to sphincter of Oddi dysfunction. Management often involves endoscopic retrograde cholangiopancreatography (ERCP) with manometry and sphincterotomy. OBJECTIVE: To determine whether endoscopic sphincterotomy reduces pain and whether sphincter manometric pressure is predictive of pain relief. DESIGN, SETTING, AND PATIENTS: Multicenter, sham-controlled, randomized trial involving 214 patients with pain after cholecystectomy without significant abnormalities on imaging or laboratory studies, and no prior sphincter treatment or pancreatitis randomly assigned (August 6, 2008-March 23, 2012) to undergo sphincterotomy or sham therapy at 7 referral medical centers. One-year follow-up was blinded. The final follow-up visit was March 21, 2013. INTERVENTIONS: After ERCP, patients were randomized 2:1 to sphincterotomy (n = 141) or sham (n = 73) irrespective of manometry findings. Those randomized to sphincterotomy with elevated pancreatic sphincter pressures were randomized again (1:1) to biliary or to both biliary and pancreatic sphincterotomies. Seventy-two were entered into an observational study with conventional ERCP managemeny. MAIN OUTCOMES AND MEASURES: Success of treatment was defined as less than 6 days of disability due to pain in the prior 90 days both at months 9 and 12 after randomization, with no narcotic use and no further sphincter intervention. RESULTS: Twenty-seven patients (37%; 95% CI, 25.9%-48.1%) in the sham treatment group vs 32 (23%; 95% CI, 15.8%-29.6%) in the sphincterotomy group experienced successful treatment (adjusted risk difference, -15.6%; 95% CI, -28.0% to -3.3%; P = .01). Of the patients with pancreatic sphincter hypertension, 14 (30%; 95% CI, 16.7%-42.9%) who underwent dual sphincterotomy and 10 (20%; 95% CI, 8.7%-30.5%) who underwent biliary sphincterotomy alone experienced successful treatment. Thirty-seven treated patients (26%; 95% CI,19%-34%) and 25 patients (34%; 95% CI, 23%-45%) in the sham group underwent repeat ERCP interventions (P = .22). Manometry results were not associated with the outcome. No clinical subgroups appeared to benefit from sphincterotomy more than others. Pancreatitis occurred in 15 patients (11%) after primary sphincterotomies and in 11 patients (15%) in the sham group. Of the nonrandomized patients in the observational study group, 5 (24%; 95% CI, 6%-42%) who underwent biliary sphincterotomy, 12 (31%; 95% CI, 16%-45%) who underwent dual sphincterotomy, and 2 (17%; 95% CI, 0%-38%) who did not undergo sphincterotomy had successful treatment. CONCLUSIONS AND RELEVANCE: In patients with abdominal pain after cholecystectomy undergoing ERCP with manometry, sphincterotomy vs sham did not reduce disability due to pain. These findings do not support ERCP and sphincterotomy for these patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00688662.