美国南卡罗来纳医科大学B Joseph Elmunzer团队比较了吲哚美辛联合不联合胰腺支架对ERCP术后胰腺炎的预防作用。该项研究成果发表在2024年1月11日出版的《柳叶刀》杂志上。

医师建议在高危患者经内镜逆行胰胆管造影术（ERCP）后，将吲哚美辛直肠给药和放置预防性胰腺支架相结合，以预防胰腺炎。初步证据表明，吲哚美辛的使用可能会消除或大大减少支架置入的需要，支架置入是一种技术复杂、成本高昂且潜在有害的干预措施。

研究组在美国和加拿大20个转诊中心进行了一项随机、非劣效性试验，将ERCP术后胰腺炎高危患者（年龄≥18岁）随机分配（1:1）接受单独的直肠吲哚美辛或吲哚美辛联合预防性胰腺支架治疗。患者、治疗临床医生和结果评估员均双盲。主要结局为ERCP术后胰腺炎。为了宣布非劣效性，在意向治疗人群和方案人群中，ERCP术后胰腺炎（单独吲哚美辛与吲哚美辛加支架）差异的双侧95%置信区间的上限必须小于5%（非劣效界限）。

2015年9月17日至2023年1月25日，共有1950名患者被随机分配。单用吲哚美辛组975例患者中有145例（14.9%）发生ERCP术后胰腺炎，吲哚美辛加支架组975名患者中有110例（11.3%）发生ERCP术后胰腺炎（风险差异3.6%；95%CI 0.6-6.6；非劣效性p=0.018）。

对两组之间风险差异的事后意向治疗分析显示，单独使用吲哚美辛不如联合使用吲哚美辛加预防性支架（p=0.011）。支架置入的相对益处在各研究亚组中总体一致，但在胰腺炎高危患者中更为突出。安全性结局（严重不良事件、重症监护病房入院和住院时间）在各组之间没有差异。

研究结果表明，对于高危患者ERCP术后胰腺炎的预防，单独使用吲哚美辛的策略不如使用吲哚美辛加预防性胰腺支架的策略有效。根据临床实践指南，这些结果支持高危患者除了直肠给予吲哚美辛外，还进行预防性胰腺支架置入。

附：英文原文

Title: Indomethacin with or without prophylactic pancreatic stent placement to prevent pancreatitis after ERCP: a randomised non-inferiority trial

Author: B Joseph Elmunzer, Lydia D Foster, Jose Serrano, Gregory A Coté, Steven A Edmundowicz, Sachin Wani, Raj Shah, Ji Young Bang, Shyam Varadarajulu, Vikesh K Singh, Mouen Khashab, Richard S Kwon, James M Scheiman, Field F Willingham, Steven A Keilin, Georgios I Papachristou, Amitabh Chak, Adam Slivka, Daniel Mullady, Vladimir Kushnir, James Buxbaum, Rajesh Keswani, Timothy B Gardner, Nauzer Forbes, Amit Rastogi, Andrew Ross, Joanna Law, Patrick Yachimski, Yen-I Chen, Alan Barkun, Zachary L Smith, Bret Petersen, Andrew Y Wang, John R Saltzman, Rebecca L Spitzer, Collins Ordiah, Cathie Spino, Valerie Durkalski-Mauldin, B. Joseph Elmunzer, Lydia D. Foster, Jose Serrano, Gregory A. Coté, Steven A. Edmundowicz, Sachin Wani, Raj Shah, Ji Young Bang, Shyam Varadarajulu, Vikesh K. Singh, Mouen Khashab, Richard S. Kwon, James M. Scheiman, Field F. Willingham, Steven A. Keilin, Georgios I. Papachristou, Amitabh Chak, Adam Slivka, Daniel Mullady, Vladimir Kushnir, James Buxbaum, Rajesh Keswani, Timothy B. Gardner, Nauzer Forbes, Amit Rastogi, Andrew Ross, Joanna Law, Patrick Yachimski, Yen-I Chen, Alan Barkun, Zachary L. Smith, Bret Petersen, Andrew Y. Wang, John R. Saltzman, Rebecca L. Spitzer, Collins Ordiah, Cathie Spino, Peter D.R. Higgins, Erin Forster, Robert A. Moran, Brian Brauer, Erik J. Wamsteker, Qiang Cai, Emad Qayed, Royce Groce, Somashekar G. Krishna, Ashley Faulx, Brooke Glessing, Mordechai Rabinovitz, Gabriel Lang, Aziz Aadam, Srinadh Komanduri, Jefferey Adler, Stuart Gordon, Rachid Mohamed, Mojtaba Olyaee, April Wood-Williams, Emily K. Depue Brewbaker, Andre Thornhill, Mariana Gould, Kristen Clasen, Jama Olsen, Violette C. Simon, Ayesha Kamal, Sarah L. Volk, Ambreen A. Merchant, Ali Lahooti, Nancy Furey, Gulsum Anderson, Thomas Hollander, Alejandro Vazquez, Thomas Y. Li, Steven M. Hadley

Issue&Volume: 2024-01-11

Abstract:

Background

The combination of rectally administered indomethacin and placement of a prophylactic pancreatic stent is recommended to prevent pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients. Preliminary evidence suggests that the use of indomethacin might eliminate or substantially reduce the need for stent placement, a technically complex, costly, and potentially harmful intervention.

Methods

In this randomised, non-inferiority trial conducted at 20 referral centres in the USA and Canada, patients (aged ≥18 years) at high risk for post-ERCP pancreatitis were randomly assigned (1:1) to receive rectal indomethacin alone or the combination of indomethacin plus a prophylactic pancreatic stent. Patients, treating clinicians, and outcomes assessors were masked to study group assignment. The primary outcome was post-ERCP pancreatitis. To declare non-inferiority, the upper bound of the two-sided 95% CI for the difference in post-ERCP pancreatitis (indomethacin alone minus indomethacin plus stent) would have to be less than 5% (non-inferiority margin) in both the intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov (NCT02476279), and is complete.

Findings

Between Sept 17, 2015, and Jan 25, 2023, a total of 1950 patients were randomly assigned. Post-ERCP pancreatitis occurred in 145 (14·9%) of 975 patients in the indomethacin alone group and in 110 (11·3%) of 975 in the indomethacin plus stent group (risk difference 3·6%; 95% CI 0·6–6·6; p=0·18 for non-inferiority). A post-hoc intention-to-treat analysis of the risk difference between groups showed that indomethacin alone was inferior to the combination of indomethacin plus prophylactic stent (p=0·011). The relative benefit of stent placement was generally consistent across study subgroups but appeared more prominent among patients at highest risk for pancreatitis. Safety outcomes (serious adverse events, intensive care unit admission, and hospital length of stay) did not differ between groups.

Interpretation

For preventing post-ERCP pancreatitis in high-risk patients, a strategy of indomethacin alone was not as effective as a strategy of indomethacin plus prophylactic pancreatic stent placement. These results support prophylactic pancreatic stent placement in addition to rectal indomethacin administration in high-risk patients, in accordance with clinical practice guidelines.

DOI: 10.1016/S0140-6736(23)02356-5

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)02356-5/abstract