Rectal Indomethacin Versus Rectal Indomethacin and Sublingual Nitrate to Prevent Post-ERCP Pancreatitis: a Multicentre, Non-inferiority, Double-blind, Randomised Trial
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 2,700
- 试验地点
- 4
- 主要终点
- Rate of post-ERCP Pancreatitis
研究概览
简要总结
Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) are at risk for post-ERCP pancreatitis (PEP), which is associated with adverse outcomes. Combination prophylaxis strategies are increasingly investigated to prevent PEP more effectively, and studies have confirmed the benefits. Two randomized controlled trials revealed that combination prophylaxis with rectal NSAIDs and sublingual nitrate has reduced PEP rates to 5.6%-6.7% in average-risk patients. However, there was concern regarding the safety of sublingual nitrate with reports of significant increasing the risk of hypotesion (rate of 54.9%) and headache (rate of 4.1%) as compared with placebo.
As a safety drug, rectal administration of one dose NSAIDs is recommended as basic chemoprophylaxis in common or high-risk patients in guidelines. Results from previous studies showed rectal administration of NSAIDs significantly reduced PEP rate to 4-5.3% in average-risk patients. Although the difference in demographics, study design and outcomes definition, evidence was obtained that rectal NSAIDS was associated with similar PEP rate as combination prophylaxis with rectal NSAIDs and sublingual nitrate. However, evidence is lacking from large, randomized clinical trials indicating that efficiency of PEP prevention with rectal NSAIDs alone is not inferior to with combination prophylaxis. The investigators conduct this trial to investigate the hypothesis that rectal NSAIDs alone is non-inferior to the combination prophylaxis in terms of PEP prevention, but with reduce side effect.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients (age, 18-80 y) with native papilla planned for diagnostic or therapeutic ERCP were eligible for enrollment in the study.
排除标准
- •contraindications to ERCP;
- •allergy to nitrates or NSAIDs;
- •currently on nitrate medication;
- •receiving NSAIDs within 7 days;
- •not suitable for indomethacin eg, gastrointestinal hemorrhage within the past 4 weeks, renal dysfunction (creatinine level >1.4 mg/dL) or the presence of coagulopathy before the procedure (international normalized ratio > 1.5);
- •acute pancreatitis within 3 days;
- •pregnant or breastfeeding women;
- •unwilling or inability to provide consent.
研究组 & 干预措施
Rectal indomethacin and sublingual placebo
All patients without contraindications should receive sublingual placebo within 5 min before ERCP.
All patients without contraindications should receive rectal indomethacin within 30 min before ERCP.
干预措施: Indomethacin 100 MG (Drug)
Rectal indomethacin and sublingual nitrate
All patients without contraindications should receive sublingual isosorbide dinitrate within 5 min before ERCP.
All patients without contraindications should receive rectal indomethacin within 30 min before ERCP.
干预措施: Isosorbide Dinitrate 5 MG (Drug)
Rectal indomethacin and sublingual nitrate
All patients without contraindications should receive sublingual isosorbide dinitrate within 5 min before ERCP.
All patients without contraindications should receive rectal indomethacin within 30 min before ERCP.
干预措施: Indomethacin 100 MG (Drug)
Rectal indomethacin and sublingual placebo
All patients without contraindications should receive sublingual placebo within 5 min before ERCP.
All patients without contraindications should receive rectal indomethacin within 30 min before ERCP.
干预措施: Sublingual Placebo (Drug)
Rectal placebo and sublingual nitrate
All patients without contraindications should receive sublingual isosorbide dinitrate within 5 min before ERCP.
All patients without contraindications should receive rectal placebo within 30 min before ERCP.
干预措施: Isosorbide Dinitrate 5 MG (Drug)
Rectal placebo and sublingual nitrate
All patients without contraindications should receive sublingual isosorbide dinitrate within 5 min before ERCP.
All patients without contraindications should receive rectal placebo within 30 min before ERCP.
干预措施: Rectal placebo (Drug)
Rectal placebo and sublingual placebo
All patients without contraindications should receive sublingual placebo within 5 min before ERCP.
All patients without contraindications should receive rectal placebo within 30 min before ERCP.
干预措施: Sublingual Placebo (Drug)
Rectal placebo and sublingual placebo
All patients without contraindications should receive sublingual placebo within 5 min before ERCP.
All patients without contraindications should receive rectal placebo within 30 min before ERCP.
干预措施: Rectal placebo (Drug)
结局指标
主要结局
Rate of post-ERCP Pancreatitis
时间窗: 14 days
The diagnosis of PEP was established if there was new onset of upper abdominal pain associated with an increased amylase or lipase level of at least 3 times the upper limit of normal range at 24 hours after the procedure, and hospitalization for at least 2 nights. Doctors are advised to use cross-sectional imaging to identify ambiguous PEP.
次要结局
- Other adverse events(14 days)
- Rate of moderate to severe PEP(14 days)
研究者
Yanglin Pan
Associated professor
Air Force Military Medical University, China