A Randomized Trial of Rectal Indomethacin and Papillary Spray of Epinephrine Versus Rectal Indomethacin to Prevent Post-ERCP Pancreatitis in High Risk Patients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 948
- 试验地点
- 4
- 主要终点
- Number of Patients Who Developed Post-ERCP Pancreatitis
研究概览
简要总结
This research is being done to see if using a combination of rectal indomethacin and epinephrine spray during endoscopy, can prevent pancreatitis that may occur after ERCP (a type of gastrointestinal endoscopy).
详细描述
Background: Post-ERCP pancreatitis (PEP) is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP) with an estimated incidence of 3-7% among average risk patients and 15-20% among patients at high risk for developing PEP. Around 500,000 - 700,000 ERCPs are performed annually in U.S. Even with a modest incidence of 5%, PEP results in approximately $150 million in healthcare costs in the US alone.
A recent landmark controlled trial demonstrated the superiority of rectal nonsteroidal antiinflammatory drug - NSAIDs (indomethacin) over placebo in preventing PEP among patients at high risk for PEP. Also, epinephrine sprayed on the major duodenal papilla was shown to reduce the incidence of PEP in multiple studies. Our group performed a network meta-analysis (NMA) which simultaneously compared 16 drugs evaluated in 99 randomized controlled trials with 25,313 patients, to determine their relative efficacy using direct and indirect comparisons. Interestingly, the NMA ranked epinephrine as the best performing drug, followed by rectal NSAIDs and nafamostat.
Indomethacin acts on pancreatic inflammation while epinephrine sprayed on duodenal papilla keeps the pancreatic duct open by reducing papillary edema. The use of these drugs in combination may potentially synergistically reduce or further reduce the incidence of PEP.
Hypothesis: A combination of papillary spray of epinephrine and rectal indomethacin is superior to the use of rectal indomethacin alone, for PEP prophylaxis among patients at high risk for PEP.
Sample size justification: Based on the information from earlier controlled trials, the Investigators assume that PEP incidence will be 10% in the rectal NSAID arm (Group A) and it will be reduced to 5% by the additional use of papillary spray of epinephrine (Group B). Therefore, a total of 474 patients in each arm, or 948 patients in total, will be required to see a 50% difference between the groups with a power of 0.8 and two sided alpha of 0.05.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Major inclusion criteria (If patients meet at least 1 of the criteria):
- •History of PEP
- •Pancreatic sphincterotomy
- •Pre-cut sphincterotomy
- •Difficult cannulation (>5 attempts / 10 minutes to cannulate)
- •Failed cannulation
- •Pneumatic dilation of an intact sphincter
- •Sphincter of Oddi dysfunction of Type I or Type II
- •Minor inclusion criteria (If patients meet at least 2 of the criteria):
- •Age < 50 & Female gender
- •History of acute pancreatitis (at least 2 episodes)
- •>/= 3 pancreatic injections (with at least 1 injection in tail)
- •Pancreatic acinarization
- •Pancreatic Brush Cytology
排除标准
- •Unwillingness or inability to consent for the study
- •Age < 18 years
- •Intrauterine pregnancy
- •Breastfeeding mother
- •Standard contraindications to ERCP
- •Allergy / hypersensitivity to aspirin or NSAIDs or epinephrine
- •Chronic renal disease (Cr > 1.4)
- •Active or recent (within 4 weeks) gastrointestinal hemorrhage
- •Acute pancreatitis (lipase peak) within 72 hours
- •Known chronic calcific pancreatitis
- •Pancreatic head mass
- •Receiving pancreatic duct stent placement for any indication
- •Procedure performed on major papilla/ventral pancreatic duct in patients with pancreas divisum
- •ERCP for pancreatic/biliary stent removal or exchange without anticipated pancreatogram
- •Subject with prior biliary sphincterotomy now scheduled for repeat biliary therapy without anticipated pancreatogram
- •Anticipated inability to follow protocol
- •Sphincter of Oddi dysfunction of Type III
研究组 & 干预措施
Rectal Indomethacin only
Patients in this group will receive 20 ml of normal saline sprayed on the duodenal papilla and surrounding regions of edema, over a period of 1 minute using any ERCP cannulation catheter, at the end of procedure, just before the withdrawal of endoscope; followed by 100 mg of rectal indomethacin.
干预措施: Rectal Indomethacin (Drug)
Rectal Indomethacin plus papillary spray of Epinephrine
Patients in this group will receive 20 ml of 0.02% epinephrine sprayed on the duodenal papilla and surrounding regions of edema, over a period of 1 minute using any ERCP cannulation catheter, at the end of procedure, just before the withdrawal of endoscope; followed by 100 mg of rectal indomethacin.
干预措施: Rectal Indomethacin (Drug)
Rectal Indomethacin plus papillary spray of Epinephrine
Patients in this group will receive 20 ml of 0.02% epinephrine sprayed on the duodenal papilla and surrounding regions of edema, over a period of 1 minute using any ERCP cannulation catheter, at the end of procedure, just before the withdrawal of endoscope; followed by 100 mg of rectal indomethacin.
干预措施: Epinephrine (Drug)
结局指标
主要结局
Number of Patients Who Developed Post-ERCP Pancreatitis
时间窗: 24 hours after ERCP
The primary outcome variable of interest is the incidence of post ERCP pancreatitis (PEP) as defined by the consensus guidelines as 1) New or increased abdominal pain that is clinically consistent with a syndrome of acute pancreatitis and 2) amylase or lipase ≥ 3x the upper limit of normal 24 hours after the procedure and 3) Hospitalization or prolongation of existing hospitalization for at least 2 days.
次要结局
- Number of Patients Who Developed Severe Post-ERCP Pancreatitis(up to 30 days after ERCP)