Optimal Timing of Endoscopic Intervention in the Treatment of Chronic Pancreatitis.

Study Overview
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Brief Summary
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This study aims to determine the optimal timing of endoscopic intervention after extracorporeal shock wave lithotripsy(ESWL) of chronic pancreatitis with pancreatic stones.

Detailed Description
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Chronic pancreatitis（CP）is a chronic progressive fibro-inflammatory disease of the pancreas induced by a wide range of factors including genetic and environmental elements, with recurrent abdominal pain and pancreatic secretion insufficiency as its major clinical signs. Chronic pancreatitis is not only a tough disease of the gastrointestinal system but also a worldwide medical problem. At present, the MESS (medicine-extracorporeal shock wave lithotripsy-endoscopic retrograde cholangiopancreatography-surgery）formed by changhai hospital in CP diagnosis and treatment is gradually becoming mature, and the clinical effect of this system is obvious. However, there are still some difficulties and knowledge gaps in the clinical treatment of CP. Currently, it is recommended by both domestic and foreign guidelines that ERCP combined with ESWL as the first-line treatment pattern for patients with chronic pancreatitis associate pain. It has previously been observed that ERCP performed less than 2 days after ESWL may be more likely to fail, possibly owing to ESWL-induced edema. However, there is no high-quality research to demonstrate how to choose the most optimal timing of ERCP after ESWL for patients with indications for endoscopic treatment. This prospective, randomized controlled research has therefore aimed to determine the most optimal timing of ERCP after ESWL. Patients with painful chronic pancreatitis and pancreatic stones larger than 5 mm in diameter will be randomly and equally assigned to three groups, which are divided according to the time interval between ESWL and ERCP, including <12 hours subgroup, 12 36 hours subgroup and >36 hours subgroup. The cannulation success rate and stone clearance rate of the pancreatic duct will be assessed in each group to explore the most appropriate timing of ERCP, and then provide an important reference basis for the clinical treatment of chronic pancreatitis.

Official Title
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Optimal Timing of Endoscopic Intervention After Extracorporeal Shock-Wave Lithotripsy in the Treatment of Chronic Pancreatitis With Pancreatic Stones.

Conditions
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Pancreatitis, Chronic

Intervention / Treatment
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* Procedure: time interval between ESWL and ERCP is 12h
* Procedure: time interval between ESWL and ERCP is 12-36h
* Procedure: time interval between ESWL and ERCP is greater than 36h
* Drug: morphine, buprenorphine, pethidine, tramaldol, metamizole and acetylsalicylacid (Analgesics)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: symptomatic adult patients diagnosed with chronic pancreatitis and main pancreatic duct positive stones（>5mm in diameter） no ERCP and ESWL history before the admission provides informed consent Exclusion Criteria: suspected to have malignant tumors; history of pancreatic surgery or gastrojejunostomy (Billroth II); with end-stage disease; with contraindications to ESWL or ERCP, such as pregnancy, abdominal aortic aneurysm, etc. acute pancreatitis within 3 days pancreatic ascites

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Endoscopic group <12h<br>The patients received intravenous analgesia (flurbiprofen and remifentanil) before the ESWL (Compact Delta II; Dornier Med Tech, Wessling, Germany). After the last ESWL session, the patients are treated with following ERCP within 12h. ERCP was performed under conscious sedation with intramuscular administration of diazepam 2.5-5.0 mg and pethidine 25-50 mg. If necessary, endoscopic sphincterotomy was performed. A dilating bougie or balloon will be used to dilate the stenosis after sphincterotomy. Standard techniques (i.e., extraction basket, extraction balloon, or both) will be used for stone removal. A pancreatic duct stent for drainage and nasopancreatic catheters will be inserted for temporary drainage if necessary. | Procedure: time interval between ESWL and ERCP is 12h<br>* The patients received intravenous analgesia before the ESWL. After the last ESWL session, the patients are treated with following ERCP within 12h.<br>* Other names: ERCP;Drug: morphine, buprenorphine, pethidine, tramaldol, metamizole and acetylsalicylacid (Analgesics)<br>* Analgesics administrated include morphine, buprenorphine, pethidine, tramaldol, metamizole and acetylsalicylacid. They will only be administrated as needed.<br>|
| Active Comparator: Endoscopic group 12-36h<br>The patients received intravenous analgesia (flurbiprofen and remifentanil) before the ESWL (Compact Delta II; Dornier Med Tech, Wessling, Germany). After the last ESWL session, the patients are treated with following ERCP within 12-36h. ERCP was performed under conscious sedation with intramuscular administration of diazepam 2.5-5.0 mg and pethidine 25-50 mg. If necessary, endoscopic sphincterotomy was performed. A dilating bougie or balloon will be used to dilate the stenosis after sphincterotomy. Standard techniques (i.e., extraction basket, extraction balloon, or both) will be used for stone removal. A pancreatic duct stent for drainage and nasopancreatic catheters will be inserted for temporary drainage if necessary. | Procedure: time interval between ESWL and ERCP is 12-36h<br>* The patients received intravenous analgesia before the ESWL. After the last ESWL session, the patients are treated with following ERCP within 12-36h.<br>* Other names: ERCP;Drug: morphine, buprenorphine, pethidine, tramaldol, metamizole and acetylsalicylacid (Analgesics)<br>* Analgesics administrated include morphine, buprenorphine, pethidine, tramaldol, metamizole and acetylsalicylacid. They will only be administrated as needed.<br>|
| Active Comparator: Endoscopic group >36h<br>The patients received intravenous analgesia (flurbiprofen and remifentanil) before the ESWL (Compact Delta II; Dornier Med Tech, Wessling, Germany). The time scale between the last ESWL session and following ERCP is greater than 36h. ERCP was performed under conscious sedation with intramuscular administration of diazepam 2.5-5.0 mg and pethidine 25-50 mg. If necessary, endoscopic sphincterotomy was performed. A dilating bougie or balloon will be used to dilate the stenosis after sphincterotomy. Standard techniques (i.e., extraction basket, extraction balloon, or both) will be used for stone removal. A pancreatic duct stent for drainage and nasopancreatic catheters will be inserted for temporary drainage if necessary. | Procedure: time interval between ESWL and ERCP is greater than 36h<br>* The patients received intravenous analgesia before the ESWL. After the last ESWL session, the patients are treated with following ERCP >36h.<br>* Other names: ERCP;Drug: morphine, buprenorphine, pethidine, tramaldol, metamizole and acetylsalicylacid (Analgesics)<br>* Analgesics administrated include morphine, buprenorphine, pethidine, tramaldol, metamizole and acetylsalicylacid. They will only be administrated as needed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful MPD Cannulation Rates | technical success rate of pancreatic cannulation | during ERCP procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful clearance of MPD stones | Ductal clearance has been defined as complete, partial, or unsuccessful if the proportion of stones cleared was > 90 %, 50 %-90 %, or < 50 %, respectively. | during ERCP procedure | 
| post-ERCP complications | Major post-ERCP complications includes post-ERCP pancreatitis, bleeding, infection, and perforation, which are classified as mild, moderate, or severe, depending mainly on the length of hospitalization and the need for invasive treatment. | 30 days | 
| severity of post-ERCP complications | severity are classified as mild, moderate, or severe, depending mainly on the length of hospitalization and the need for invasive treatment. | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Extracorporeal Shock Wave Lithotripsy(ESWL), Chronic pancreatitis, Endoscopic Retrograde Cholangiopancreatography(ERCP), Pancreatic stones