Stent vs. indomethacin for preventing post-ERCP pancreatitis (SVI study)

背景：胰腺炎是内窥镜逆行胰胆管造影（ERCP）最常见的并发症，发病率高，偶尔死亡，医疗费用增加。直到最近，预防ercp后胰腺炎（PEP）的唯一有效方法是预防性胰腺支架置入术（PSP），这是一种昂贵、耗时且技术上具有挑战性的干预措施。此外，尝试放置支架可能是危险的，因为PSP的失败实际上增加了胰腺炎的风险。我们最近报道了一项大规模随机对照试验的结果，该试验表明直肠吲哚美辛（一种非甾体抗炎药）降低了高危患者ERCP后胰腺炎的风险，其中大多数（约80%）接受了胰腺支架。该RCT的二次分析表明，即使在调整了受试者风险的潜在差异后，单独使用吲哚美辛的受试者发生PEP的可能性低于单独使用胰腺支架或联合使用吲哚美辛和支架的受试者。如果吲哚美辛能够避免PSP的需要，ERCP实践的主要临床和成本效益可以实现。目的：为开展多中心临床研究评估吲哚美辛能否替代PSP预防高危患者PEP提供必要条件。方法：我们建议进行直肠用吲哚美辛单用与直肠用吲哚美辛联合预防性胰腺支架置入术预防高危患者ercp后胰腺炎的多中心非效性比较研究。180名通常接受胰腺支架预防的PEP高风险受试者将被随机分配到单独使用吲哚美辛或联合使用吲哚美辛和PSP。比较发生PEP和中重度PEP的患者比例。U34资助期的目的是在六个临床站点建立必要的研究基础设施、研究计划、数据库以及科学、后勤和监管文件，以完成一项大容量、多中心、比较吲哚美辛单独与直肠吲哚美辛联合预防性胰腺支架置入的比较有效性研究。此外，我们的目标是为研究对象获得的生物标本建立一个高标准、有质量保证的中央储存库，以便将来进行PEP预防的转化研究。

DESCRIPTION (provided by applicant): Background: Pancreatitis is the most frequent complication of endoscopic retrograde cholangiopancreatography (ERCP), accounting for substantial morbidity, occasional mortality, and increased health care expenditures. Until recently, the only effective method of preventing post-ERCP pancreatitis (PEP) had been prophylactic pancreatic stent placement (PSP), an intervention that is costly, time consuming, and technically challenging. Further, attempting to place a stent can be dangerous because failure of PSP actually increases the risk of pancreatitis above baseline. We recently reported the results of a large-scale randomized controlled trial demonstrating that rectal indomethacin, a non-steroidal anti-inflammatory drug, reduced the risk of pancreatitis after ERCP in high-risk patients, most of whom (>80%) had received a pancreatic stent. Secondary analysis of this RCT suggested that subjects who received indomethacin alone were less likely to develop PEP than those who received a pancreatic stent alone or the combination of indomethacin and stent, even after adjusting for underlying differences in subject risk. If indomethacin were to obviate the need for PSP, major clinical and cost benefits in ERCP practice could be realized. Objective: To develop all the necessary elements to conduct a multi-center clinical study evaluating whether indomethacin can replace PSP for preventing PEP in high-risk patients. Methods: We are proposing a comparative effectiveness multi-center non-inferiority study of rectal indomethacin alone vs. the combination of rectal indomethacin and prophylactic pancreatic stent placement for the prevention of post-ERCP pancreatitis in high-risk patients. One thousand and eighty subjects at elevated risk for PEP who would normally receive a pancreatic stent for prophylaxis will be randomized to indomethacin alone or the combination of indomethacin and PSP. The proportion of patients developing PEP and moderate- severe PEP will be compared. The aim of the U34 funding period is to develop, at six clinical sites, the necessary study infrastructure, research plan, database, and scientific, logistic, and regulatory documents to complete a large-volume, multi-center, comparative effectiveness study comparing indomethacin alone vs. the combination of rectal indomethacin and prophylactic pancreatic stent placement. In addition, we aim to establish a high standard, quality-assured central repository for biological specimens acquired from study subjects on which future translational studies of PEP prevention can be conducted.