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CompletedNCT02515474Updated Jan 5, 2024

Comparison of LCBDE vs ERCP + LC for Choledocholithiasis

An interventional study of Laparoscopy and Endoscopy in Choledocholithiasis, sponsored by Hepatopancreatobiliary Surgery Institute of Gansu Province. Completed at 12 sites in China. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2024-01-05.

Sponsored by Hepatopancreatobiliary Surgery Institute of Gansu Province · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
1,000
Allocation
Non-randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Choledocholithiasis

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Keywords

  • Cholangiopancreatography
  • Endoscopic
  • Common bile duct
  • Complication
  • Recurrence
  • Laparoscopic
03

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
Single (Participant)
Enrollment
1,000 participants (actual)

Study arms

  • Active comparator
    LCBDE group (single step)

    Choledocholithiasis patient, after Laparoscopic Cholecystectomy (LC) to remove the gallbladder, Laparoscopic Common Bile Duct Exploration (LCBDE) was performed for removing the bile duct stone(s) in laparoscopy. Choledochoscope detection or cholangiograms should be chosen as a method of obtain stone clearance. T-tube was acceptable if needed.

    Procedure: Laparoscopy

  • Active comparator
    ERCP group (sequential step)

    Choledocholithiasis patient, Endoscopic Retrograde cholangiopancreatography (ERCP) was performed for removing the bile duct stone(s) in endoscopy prior to Laparoscopic Cholecystectomy (LC). Sphincterotomy (EST) and Endoscopic papillary balloon dilatation (EPBD) can be chosen accordingly. The laparoscopic cholecystectomy was subsequently performed as soon as technically feasible following the ERCP in one month.

    Procedure: Endoscopy

Interventions

  • ProcedureLaparoscopy

    After removing the gallbladder, Laparoscopic common bile duct exploration (LCBDE) was performed by one fulltime attending in laparoscopy in a routine fashion. Access from the opening of the anterior wall of common bile duct or from the dilated cystic duct was acceptable, removed stone(s) and irrigated the duct followed by choledochoscope detection simultaneously. Cholangiograms were also can be a alternative method to obtain stone clearance. If needed, all fluoroscopy was performed by the principal author in the presence of and concurrence with the ERCP endoscopist. Once the LCBDE was completed, the incision of the bile duct was sewed intermittently by absorbed threads, or ligated cystic duct. T-tube was acceptable if needed.

    Also known as: Laparoscopic common bile duct exploration (LCBDE)

  • ProcedureEndoscopy

    Initially endoscopic retrograde cholangiopancreatography (ERCP) was performed by a fulltime attending and concurrence of the principal author in endoscopy. Patients randomized to ERCP+ LC group were scheduled to undergo the endoscopic procedure using fluoroscopy in the endoscopy center under moderate sedation (principally intravenous midazolam and meperidine) prior to the intended laparoscopy. Gastric intestinal atony during ERCP was routinely achieved using scopolamine butylbromide injection. Sphincterotomy (EST) and Endoscopic papillary balloon dilatation (EPBD) can be choose accordingly. The laparoscopic cholecystectomy was subsequently performed as soon as technically feasible following the ERCP in one month.

    Also known as: Endoscopic Retrograde cholangiopancreatography (ERCP)

05

What researchers measure

Primary outcomes

  1. Common bile duct stone recurrence

    Stone was diagnosed by MRI or CT whenever be confirmed after 3 months after procedures.

    Time frame: Up to 5 years

Secondary outcomes

  1. The proportion of patients with all stones removed

    Time frame: Up to 8 hours

  2. Operation time

    For arm1 (LCBED): the whole process of the operation; for arm2 (LC+ERCP): the total of the two procedures, LC and ERCP

    Time frame: Up to 8 hours

  3. Length of stay in hospital

    Time frame: Up to 60 days

  4. The total hospitalization costs

    Time frame: Up to 60 days

  5. Upper abdominal pain after each procedure by Numerical Rating Scale

    Time frame: Up to 60 days

  6. Hemorrhage

    Maintained positive fecal occult blood test appears or Hb decreased by 10g/l

    Time frame: Up to 60 days

  7. Perforation

    CT scan shows retroperitoneal space fluid or gas

    Time frame: Up to 7 days

  8. Acute cholangitis

    Intermittent chills and fever after procedures

    Time frame: Up to 5 years

  9. Bile leakage

    Any bile juice aspirated from the abdominal cavity after procedures

    Time frame: Up to 60 days

  10. Stricture of the bile duct

    Any stricture appears after the procedures

    Time frame: Up to 5 years

  11. Number of Death connected with the procedures and complications

    Time frame: Up to 5 years

06

Study locations

12 sites
  • The first hospital of Lanzhou University
    Lanzhou, Gansu 730000, China
  • Union hospital,Tongji medical collage,Huazhong University of science and technology
    Wuhan, Hubei 430022, China
  • Second Xiangya Hospital, Central South University
    Changsha, Hunan 410011, China
  • The First Hospital of Jilin University
    Changchun, Jilin 130021, China
  • General Hospital of Ningxia Medical University
    Yinchuan, Ningxia 750004, China
  • Shandong jiaotong Hospital
    Jinan, Shandong 250000, China
  • The first affiliated hospital of Xi 'an jiaotong university
    Xi'an, Shanxi 710061, China
  • The First Teaching Hospital of Xinjiang Medical University
    Ürümqi, Xinjiang 830054, China
  • The First Affiliated Hospital, Zhejiang University
    Hangzhou, Zhejiang 310003, China
  • Southwest Hospital of Third Military Medical University
    Chongqing, 400038, China
  • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
    Shanghai, 200092, China
  • Tianjin Nankai Hospital
    Tianjin, 300100, China
07

References and documents

Publications

  • 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. PubMed 10526025 ↗
  • 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. PubMed 24162318 ↗
  • 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. PubMed 23871320 ↗
  • 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. PubMed 20135172 ↗
  • 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. PubMed 20087351 ↗
  • 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. PubMed 19792866 ↗
  • 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. PubMed 12145577 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT02515474
Lead sponsor
Hepatopancreatobiliary Surgery Institute of Gansu Province
Responsible party
Xun Li (professor of surgery, Hepatopancreatobiliary Surgery Institute of Gansu Province) — Principal investigator
First posted
Aug 4, 2015
Start date
Sep 1, 2015
Primary completion
Jan 1, 2024
Completion
Jan 1, 2024
Last update
Jan 5, 2024

Study contacts

Xun Li, M.D., Ph.D.
principal investigator · Hepatopancreatobiliary Surgery Institute of Gansu Province

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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