Comparison of Endoscopic Sphincterotomy Plus Large-balloon Dilatation and Conventional Treatment for Large CBD Stones

Study Overview
=================
Brief Summary
-----------------
Bile duct stone extraction is impossible after endoscopic sphincterotomy (ES) alone in approximatively 10% of cases (mostly because of stones' size). Adjunction of a mechanical lithotripsy (ML) is well established to improve clearance of common bile duct (CBD) stones. Because of inconstant success, high cost, and length of procedure, an alternative method was proposed in 2003: endoscopic sphincterotomy plus large balloon dilatation (ESLBD). If the safety of ESLBD is accepted in all recent published studies, it remains controversial wether ESLBD is superior to conventional endoscopic treatment associating ES± ML for CBD stones. Procedure treatment and place of ESLBD in CBD stones therapeutic strategy is unclear. The purpose of this prospective comparative multi center randomized study is to evaluate the superiority or not of ESLBD on conventional treatment (ES±ML) for the treatment of large bile duct stone (≥13mm) after standard ES, and to propose a new CBD stones therapeutic strategy.

Official Title
-----------------
Endoscopic Sphincterotomy Plus Large-Balloon Dilatation (ESLBD) Versus Conventional Endoscopic Treatment for Removal of Large Common Bile Duct Stones : A Prospective Comparative Multi Center Randomized Study

Conditions
-----------------
Choledocholithiasis, Large Common Bile Duct Stone

Intervention / Treatment
-----------------
* Procedure: ERCP
* Procedure: Endoscopic Sphincterotomy
* Device: Large Balloon Dilatation of Oddi Sphincter
* Procedure: Stone extraction


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient with CBD stones with a smaller diameter ≥ 13mm on cholangiogram Exclusion Criteria: Active or history of acute pancreatitis Presence of intrahepatic stones History of Billroth II or roux-en-Y reconstruction Coagulation disorder (partial thromboplastin time > 42 seconds, prothrombin time (Quick value) < 50% and platelet count of <50 000/mm3) Current anticoagulation or clopidogrel treatment Pregnancy Inability to give informed consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ESLBD<br>Endoscopic Sphincterotomy plus Large Balloon Dilatation +/- lithotripsy ERCP with deep cancellation of BDS Endoscopic large sphincterotomy Large Balloon Dilatation of Oddi Sphincter: with the HERCULES, Cook 12, 15, 18 or 20 mm of diameter (adapted to stone diameter) Stone extraction with dormia basket or extraction balloon Mechanical Lithotripsy if needed | Procedure: ERCP<br>* Common bile duct cannulation with a cannulation catheter<br>* Other names: Cholangiogram with deep cannulation of CBD;Procedure: Endoscopic Sphincterotomy<br>* Endoscopic large sphincterotomy<br>* Other names: ES;Device: Large Balloon Dilatation of Oddi Sphincter<br>* Large Balloon Dilatation : with the HERCULES, Cook 12, 15, 18 or 20 mm of diameter (adapted to stone diameter)<br>* Other names: LBD, LBDS;Procedure: Stone extraction<br>* After dilatation, extraction of stones is done with dormia basket or extraction balloon and if not possible a mechanical lithotripsy is performed<br>|
| Active Comparator: CONV<br>Conventional treatment associating Endoscopic Sphincterotomy +/- Mechanical Lithotripsy (ES+/-LM) ERCP with deep cancellation of BDS Endoscopic large sphincterotomy Stone extraction with dormia basket or extraction balloon Mechanical Lithotripsy if needed | Procedure: ERCP<br>* Common bile duct cannulation with a cannulation catheter<br>* Other names: Cholangiogram with deep cannulation of CBD;Procedure: Endoscopic Sphincterotomy<br>* Endoscopic large sphincterotomy<br>* Other names: ES;Procedure: Stone extraction<br>* After dilatation, extraction of stones is done with dormia basket or extraction balloon and if not possible a mechanical lithotripsy is performed<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success of common bile duct clearance in one session of ERCP (endoscopic retrograde cholangiopancreatography) |  | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with mild or severe BLEEDING (Morbidity) after ERCP | Immediate complications were noted : bleeding : mild if blood transfusion not necessary, and severe if blood transfusion necessary Clinical data (pain, fever, vomiting...) are noted during first month Clinical examination and blood tests (Blood count, C reactive protein, lipase blood test, hepatic tests, creatininemia) were noted at the 30th day after procedure In case of bleeding suspected, a new ERCP was done Number of patients with bleeding and with any complication in both groups were noted and compared | 1 month | 
| Number of patients with mild or severe ACUTE PANCREATITIS (Morbidity) after ERCP | Immediate complications were noted : Acute pancreatitis : defined by the association of abdominal pain and lipase blood test > 3 N Severity of acute pancreatitis was evaluated on CT index, and on evolution data Clinical data (pain, fever, vomiting...) are noted during first month Clinical examination and blood tests (Blood count, C reactive protein, lipase blood test, hepatic tests, creatininemia) were noted at the 30th day after procedure Abdominal CT was performed in case of suspected acute pancreatitis Number of patients with Acute Pancreatitis and any complication in both groups were noted and compared | 1 month | 
| Number of patients with PERFORATION (Morbidity of ERCP) | Suspected on clinical data (pain, fever, vomiting...) and blood tests (Blood count, C reactive protein) noted during first day after ERCP: confirmed on CT Number of patients with perforation in both groups were noted and compared, and global morbidity in both groups were noted and compared | 1 day | 
| Number of patients with post ERCP INFECTION as angiocholitis, cholecystitis or urine infection, septicemia (Morbidity of ERCP) | Suspected on clinical data (pain, fever, vomiting...), blood tests (Blood count, C reactive protein, blood and urine cultures), noted during first day after ERCP, during 30th day and more if necessary in the meantime Abdominal US and CT were performed if necessary Number of patients with infection in both groups were noted and compared, and global morbidity in both groups were noted and compared | 1 month | 
| GLOBAL MORBIDITY of ERCP (number of patients with bleeding and/or acute pancreatistis and/or perforation and/or infection) | - Number of patients with any complication as bleeding, acute pancreatitis, perforation, infection (as angiocholitis, cholecystitis, urine infection or septicemia) happened in both groups during the first month after the procedure were noted and compared | 1 month | 
| MORTALITY of ERCP | - Number of death happened in both groups during the first month after the procedure were noted and compared | 1 month | 
| Number of patients with recurrence of BDS | Clinical data (pain, fever, vomiting...) are noted during first month Clinical examination and blood tests (Blood count, C reactive protein, lipase blood test, hepatic tests, creatininemia) were noted at the 30th day after procedure In case of recurrence BDS suspected, abdominal US and/or CT and/or MRI and/or EUS (Endoscopic Ultrasonography) were done, and if BDS was confirmed, a new ERCP was done Number of patients with recurrence of BDS in both groups in the first month after the procedure were noted and compared | 1 month | 
| Length of procedure | For each patient, time was noted at the beginning and at the end of ERCP | Day one | 
| Cost of procedure | All the instrument used during ERCP (endoscopic retrograde cholangiopancreatography) for each patient were noted, and at the end of procedure cost of all instruments were recorded | Day one | 
| comparison of the frequency of mechanical lithotripsy of both groups | In both groups mechanical lithotripsy can be performed in case of impossibility of stone extraction. The rate of lithotripsy performed in both groups were compared | Day one | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cholangiopancreatography, therapeutic strategy, Endoscopic Retrograde