Clinical trial NCT02515474: Comparison of LCBDE vs ERCP + LC for Choledocholithiasis
Official title: A Long Term Comparison of Laparoscopic Common Bile Duct Exploration and Cholecystectomy Versus Sequential ERCP Followed by Cholecystectomy for Choledocholithiasis: a Multicenter Prospected Non-randomized Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Choledocholithiasis
Keywords: Cholangiopancreatography
Endoscopic
Common bile duct
Complication
Recurrence
Laparoscopic
Lead sponsor: Hepatopancreatobiliary Surgery Institute of Gansu Province
Sponsor class: OTHER
First posted: 2015-08-04
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Protection of Oddi's sphincter remains a huge argument especially in the long term complications like common bile duct stone recurrence or cholangitis after ERCP, which determined to destroy the sphincter of Oddi. The purpose of this study is to compare the long-term outcomes of ERCP sequential LC versus LCBDE for choledocholithiasis.

Detailed description: Cholelithiasis, a common etiology factor responsible for abdominal pain, is highly prevalent worldwide. According to data from general investigation, the morbidity of cholelithiasis differs from 2.36% to 42% in different areas, and about 5% to 29% (average 18%) of all cholelithiasis cases have both gallbladder stone and common bile duct stone. In the population with age above 70 years old, 30% of which suffers from gallbladder stone in China. A causal link between the development of gallbladder stone and common bile duct stone is that 10% to 15% of gallstone patients have high potential to develop secondary common bile duct stone. In 1987, the laparoscopic cholecystectomy (LC) came into being as a revolutionary surgical method. With minimally invasive effect and high safety, LC was soon accepted as a 'Golden standard' for the treatment of gallbladder stone. Endoscopic sphincterotomy (EST) was firstly reported by Kawai and Classen in 1970. As of now, the combination of EST with other endoscopic techniques, such as basket extraction, balloon dilation and lithotripsy, have significantly improved the stone removal rate from 85% up to 90%, and ERCP has been considered as the optimal method in regard to CBD stone treatment. In 1991, the laparoscopic common bile duct exploration (LCBDE) which reflected the advantage of rigid scopes had risen to be a very promising minimally invasive alternative for the treatment of common bile duct (CBD) stone. Currently, there are mainly two kinds of minimally invasive treatments for choledocholithiasis, which refers to the "one-stage" laparoscopic method, LCBDE and the "sequential two-stage" method, ERCP followed by LC. Both methods are able to achieve the same therapeutic purpose. However, there has always been a controversy about the advantages and disadvantages due to lack of evidence from long-term follow-ups, especially the difference of long-term complications related to Oddi's sphincter functional status, which importantly refers to stone recurrence rates and cholangitis.

The potential long-term complications resulted from EST remains an issue now. It is believed that EST handles Oddi's sphincter stenosis, regurgitation cholangitis, and higher cholangiocarcinoma risks in a long run. By virtue of ERCP, multiple high stone clearance rates (87%\~97%) were reported, but meanwhile high re-ERCP rates (around 25%) were also indicated because of stone residual, and whether great stone residual rates was linked to future stone recurrence and repeated cholangitis is not clear. Several randomized controlled trial (RCT) studies had compared ERCP plus LC and LCBDE, the results were similar to the aspects of stone removal rates, costs, and patient acceptance. However, the postoperative cholangitis rate of one single center study is quite different from another. Moreover, few studies have related the stone recurrence rate in the long term follow-up. Obviously, previous RCT studies were limited by few comparison of ERCP followed by LC versus LCBDE in long-term complications, especially stone recurrence and cholangitis. Therefore, this multicenter randomize control study is designed prospectively to compare the stone recurrence and cholangitis rates between ERCP plus LC and LCBDE which can reflects the valuable of Oddi's sphincter protection during the disease management, further dedicating the treatment of gallbladder and common duct stone.

Eligibility criteria: Inclusion Criteria:

* Age 18-65 years old
* Choledocholithiasis patient did not perform any operation
* Common bile duct stone less than 2cm in maximum diameter

Exclusion Criteria:

* Unwillingness or inability to consent for the study
* Coagulation dysfunction (INR\> 1.3) and low peripheral blood platelet count (\<50×109 / L) or using anti-coagulation drugs
* Previous EST, EPBD or percutaneous transhepatic biliary drainage (PTBD)
* Prior surgery of Bismuth Ⅱ and Roux-en-Y
* Benign or malignant CBD stricture
* Preoperative coexistent diseases: acute pancreatitis, GI tract hemorrhage, severe liver disease, primary sclerosing cholangitis (PSC), septic shock
* Combined with Mirizzi syndrome and intrahepatic bile duct stones
* Malignancies
* Biliary-duodenal fistula confirmed during ERCP
* Pregnant women

Primary outcomes:
measure: Common bile duct stone recurrence
timeFrame: Up to 5 years
Secondary outcomes:
measure: The proportion of patients with all stones removed
timeFrame: Up to 8 hours
measure: Operation time
timeFrame: Up to 8 hours
measure: Length of stay in hospital
timeFrame: Up to 60 days
measure: The total hospitalization costs
timeFrame: Up to 60 days
measure: Upper abdominal pain after each procedure by Numerical Rating Scale
timeFrame: Up to 60 days
measure: Hemorrhage
timeFrame: Up to 60 days
measure: Perforation
timeFrame: Up to 7 days
measure: Acute cholangitis
timeFrame: Up to 5 years
measure: Bile leakage
timeFrame: Up to 60 days
measure: Stricture of the bile duct
timeFrame: Up to 5 years
measure: Number of Death connected with the procedures and complications
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Lanzhou
country: China
facility: The first hospital of Lanzhou University
state: Gansu
city: Wuhan
country: China
facility: Union hospital,Tongji medical collage,Huazhong University of science and technology
state: Hubei
city: Changsha
country: China
facility: Second Xiangya Hospital, Central South University
state: Hunan
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Jinan
country: China
facility: Shandong jiaotong Hospital
state: Shandong
city: Xi'an
country: China
facility: The first affiliated hospital of Xi 'an jiaotong university
state: Shanxi
city: Ürümqi
country: China
facility: The First Teaching Hospital of Xinjiang Medical University
state: Xinjiang
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University
state: Zhejiang
city: Chongqing
country: China
facility: Southwest Hospital of Third Military Medical University
city: Shanghai
country: China
facility: Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
city: Tianjin
country: China
facility: Tianjin Nankai Hospital
Study officials:
affiliation: Hepatopancreatobiliary Surgery Institute of Gansu Province
name: Xun Li, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cuschieri A, Lezoche E, Morino M, Croce E, Lacy A, Toouli J, Faggioni A, Ribeiro VM, Jakimowicz J, Visa J, Hanna GB. E.A.E.S. multicenter prospective randomized trial comparing two-stage vs single-stage management of patients with gallstone disease and ductal calculi. Surg Endosc. 1999 Oct;13(10):952-7. doi: 10.1007/s004649901145.
citation: Goh ES, Liang B, Fook-Chong S, Shahidah N, Soon SS, Yap S, Leong B, Gan HN, Foo D, Tham LP, Charles R, Ong ME. Effect of location of out-of-hospital cardiac arrest on survival outcomes. Ann Acad Med Singap. 2013 Sep;42(9):437-44.
citation: Koc B, Karahan S, Adas G, Tutal F, Guven H, Ozsoy A. Comparison of laparoscopic common bile duct exploration and endoscopic retrograde cholangiopancreatography plus laparoscopic cholecystectomy for choledocholithiasis: a prospective randomized study. Am J Surg. 2013 Oct;206(4):457-63. doi: 10.1016/j.amjsurg.2013.02.004. Epub 2013 Jul 17.
citation: Bansal VK, Misra MC, Garg P, Prabhu M. A prospective randomized trial comparing two-stage versus single-stage management of patients with gallstone disease and common bile duct stones. Surg Endosc. 2010 Aug;24(8):1986-9. doi: 10.1007/s00464-010-0891-7. Epub 2010 Feb 5.
citation: Jeon TY, Han ME, Lee YW, Lee YS, Kim GH, Song GA, Hur GY, Kim JY, Kim HJ, Yoon S, Baek SY, Kim BS, Kim JB, Oh SO. Overexpression of stathmin1 in the diffuse type of gastric cancer and its roles in proliferation and migration of gastric cancer cells. Br J Cancer. 2010 Feb 16;102(4):710-8. doi: 10.1038/sj.bjc.6605537. Epub 2010 Jan 19.
citation: Noble H, Tranter S, Chesworth T, Norton S, Thompson M. A randomized, clinical trial to compare endoscopic sphincterotomy and subsequent laparoscopic cholecystectomy with primary laparoscopic bile duct exploration during cholecystectomy in higher risk patients with choledocholithiasis. J Laparoendosc Adv Surg Tech A. 2009 Dec;19(6):713-20. doi: 10.1089/lap.2008.0428.
citation: Sgourakis G, Karaliotas K. Laparoscopic common bile duct exploration and cholecystectomy versus endoscopic stone extraction and laparoscopic cholecystectomy for choledocholithiasis. A prospective randomized study. Minerva Chir. 2002 Aug;57(4):467-74.