Rectal indometacin dose escalation for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography in high-risk patients: a double-blind, randomised controlled trial.
Rectal indometacin dose escalation for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography in high-risk patients: a double-blind, randomised controlled trial.
复制标题
DOI：
10.1016/s2468-1253(19)30337-1
复制
发表时间：
2020-02
影响因子：
35.7
通讯作者：
Elmunzer, B. Joseph
中科院分区：
文献类型：
--
作者：
Fogel, Evan L.;Lehman, Glen A.;Tarnasky, Paul;Cote, Gregory A.;Schmidt, Suzette E.;Waljee, Akbar K.;Higgins, Peter D. R.;Watkins, James L.;Sherman, Stuart;Kwon, Richard S. Y.;Elta, Grace H.;Easler, Jeffrey J.;Pleskow, Douglas K.;Scheiman, James M.;El Hajj, Ihab I.;Guda, Nalini M.;Gromski, Mark A.;McHenry, Lee, Jr.;Arol, Seena;Korsnes, Sheryl;Suarez, Alejandro L.;Spitzer, Rebecca;Miller, Marilyn;Hofbauer, Maria;Elmunzer, B. Joseph
尽管直肠给药吲哚美辛（100 mg）可有效降低高危患者内镜逆行胰胆管造影术（ERCP）后胰腺炎的发生率和严重程度，但最佳剂量尚不清楚，尽管使用，胰腺炎的发生率仍然很高。本研究的目的是比较两种吲哚美辛直肠给药方案对高危患者ERCP术后胰腺炎发生频率和严重程度的疗效。符合条件的患者是ERCP术后胰腺炎发生的高风险患者，在六个三级中心参加了一项随机双盲比较有效性试验。患者、研究人员和治疗医生对研究组分配不知情。根据研究中心分层但无其他限制的随机化时间表由不参与任何受试者临床护理的研究者计算机生成，分发给其他研究中心，并由不直接参与研究的人员保存。同一人员负责将药物和安慰剂包装在不透明信封中。主要终点是ERCP术后胰腺炎的发生。按意向治疗原则进行分析。试验注册于Clinicaltrials.gov（https：//www.clinicaltrials.gov/）：NCT 01912716，并以完成入组结束。1037例合格患者在2013年7月9日至2018年3月22日之间随机分组。141例患者（13.6%）发生胰腺炎，两组（100 mg vs 200 mg）无显著差异（76/515，14.8% vs 65/522，12.5%，P=0.32）。有19起不良事件可能归因于研究药物。1037例患者中有14例（1.4%）发生临床显著出血，标准剂量组6/515例（1.2%），高剂量组8/522例（1.5%）（P = 0.79）。3例患者发生急性肾损伤，均在高剂量组（3/522，0.6%）。ERCP后2天，标准剂量组发生非ST段抬高型心肌梗死。高剂量组在ERCP后5天发生短暂性脑缺血发作。除了141例发生ERCP术后胰腺炎的患者外，所有19例不良事件均被视为严重不良事件，因为所有不良事件均需要住院治疗。30天随访时无过敏反应或死亡。两组间出血或肾衰竭的发生率无差异。未发生过敏反应或死亡。剂量递增至200 mg直肠给药吲哚美辛与标准100 mg方案相比没有任何优势，高危患者的胰腺炎发生率仍然很高。目前的做法应继续保持不变。进一步的研究需要考虑非甾体抗炎药的药代动力学，以确定预防ERCP术后胰腺炎的最佳给药时机。这项工作得到了美国胃肠病学会临床研究奖的支持。
Although rectal indomethacin (100mg) is effective in reducing the frequency and severity of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in high-risk patients, the optimal dose is unknown and pancreatitis rates remain high despite its use. The aim of this study was to compare the efficacy of two dose regimens of rectal indomethacin on the frequency and severity of post-ERCP pancreatitis in high-risk patients. Eligible patients were those at high-risk for the development of post-ERCP pancreatitis, enrolled at six tertiary centers in a randomized double-blinded comparative effectiveness trial. Patients, study personnel, and treating physicians were blinded to study group assignment. The randomization schedule, stratified according to study center but without other restrictions, was computer-generated by an investigator uninvolved in the clinical care of any subjects, distributed to the other sites, and kept by personnel not directly involved with the study. This same personnel was responsible for packaging the drug and placebo in opaque envelopes. The primary endpoint was the development of post-ERCP pancreatitis. Analyses were conducted by intention-to-treat principle. The trial was registered with Clinicaltrials.gov (https://www.clinicaltrials.gov/): NCT01912716, and ended with complete enrollment. 1037 eligible patients were randomized between 7/9/13–3/22/18. Pancreatitis occurred in 141 patients (13.6%), with no significant difference between the two groups (100mg vs 200mg) (76/515, 14.8% vs 65/522, 12.5%, P=0.32). There were 19 adverse events that were potentially attributable to the study drug. Clinically significant bleeding occurred in 14 of the 1037 patients (1.4%), 6/515 (1.2%) in the standard-dose group and 8/522 (1.5%) in the high-dose group (P = 0.79). Three patients developed acute kidney injury developed, all in the high-dose group (3/522, 0.6%). A non-ST elevation myocardial infarction occurred in the standard-dose group 2 days after ERCP. A transient ischemic attack occurred in the high-dose group 5 days after ERCP. All 19 adverse events, in addition to the 141 patients who developed post-ERCP pancreatitis, were considered to be serious adverse events as all required hospitalization. There were no allergic reactions or deaths at the 30-day follow-up. There was no difference between the two groups regarding incidence of bleeding or renal failure. No allergic reactions or deaths occurred. Dose escalation to 200mg of rectal indomethacin does not confer any advantage over the standard 100mg regimen, with pancreatitis rates remaining high in high-risk patients. Current practice patterns should continue unchanged. Further research needs to consider the pharmacokinetics of NSAIDs to determine the optimal timing of their administration in prevention of post-ERCP pancreatitis. This work was supported by a Clinical Research Award obtained from the American College of Gastroenterology.