Interventional Endoscopy.

Abstract

Introduction: Rectal indomethacin and papillary spray of epinephrine have separately shown efficacy for the prevention of post-ERCP pancreatitis (PEP) in randomized controlled trials. We hypothesized that the combination of papillary spray of epinephrine and indomethacin may further reduce PEP over indomethacin alone. Methods: We conducted a comparative effectiveness, multicenter, double-blind, randomized trial comparing rectal indomethacin alone versus a combination of papillary spray of epinephrine and rectal indomethacin for the prevention of PEP in high risk patients. Patients with suspected sphincter of Oddi dysfunction (SOD) type 3 and those who received a pancreatic stent were excluded. Patients were randomized to receive either 100 mg of indomethacin and papillary spray of 20 mL of normal saline (indomethacin alone group) or 100 mg of indomethacin and papillary spray of 20 mL of 0.02% epinephrine (combination group) at the end of ERCP. A Data and Safety Monitoring Board conducted interim analyses with prespecified stopping rules. The primary outcome was the incidence of PEP and the secondary outcome was the severity of PEP, both defined by the consensus criteria. A total of 948 patients (474 in each group) would provide a power of 80% at a 2-sided significance level of 5% to detect a 50% difference in the rates of PEP, assuming PEP rates of 10% and 5%, respectively, for rectal indomethacin and the combination. A two-tailed Fisher's exact test was used to analyze the difference in the proportion of patients with PEP in the indomethacin alone versus the combination group. Results: A total 959 of patients (mean age 52.33±14.96 years; 551 (57.4%) females) were randomized for this trial. The baseline demographic and clinical characteristics were similar between the two groups. Females < 50 years of age (25.4%) and difficult cannulation (84.9%) were the most common patient and procedural risk factors, respectively. Trainees were involved in 24% of the cases. The incidence of PEP was 6.4% in the indomethacin alone group (n=482) compared to 6.7% in the combination group (n=477) (p=0.87). Severe PEP was found in 5 (12%) versus 7 (16%) patients in the indomethacin alone and combination groups, respectively (p=0.88). The overall mortality was 0.6% which was unrelated to the primary outcome. Conclusion: The combination of papillary spray of epinephrine and rectal indomethacin does not reduce the incidence of PEP compared to rectal indomethacin alone in high risk patients.FigureTable: Table. Association of risk factors with the incidence of PEP