Effect of ECPP on Recurrent Bile Duct Stones

Sphincterotomy, Endoscopic Clinical Trial

Official title:

Effects of Endoclip Papilloplasty and Relationship Between Post-operative Microecological Environment and Recurrent Bile Duct Stones

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05896280
• Other study ID #: LM2023425
• Status: Recruiting
• Phase: N/A
• Start date: December 1, 2022
• Est. completion date: December 31, 2023

Study information

• Verified date: October 2022
• Source: Peking University Third Hospital
• Contact: Yonghui Huang, archiater
• Phone: 13911765322
• Email: xuxiao_1028[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Endoscopic retrograde cholangiopancreatography (ERCP) combined with endoscopic papillary sphinctomy (EST) is the preferred clinical treatment for common bile duct stones, and this minimally invasive treatment technique has been widely used in clinical practice for decades. However, even after successful stone removal by EST combined with various methods, the incidence of postoperative recurrent bile duct stones can still be as high as 9.8%~30% . The emergence of these long-term complications after EST surgery is currently thought to be related to the loss of Oddi sphincter function. In clinical practice, the investigators tried a new method to repair the Oddi sphincter, that is, after ERCP+EST stone removal, a metal clip was inserted into the endoscopic clamp through the duodenoscopy, and clamp precisely on both lateral edges of the nipple after incision. This procedure is called endoscopic nipple clipping (ECPP). Initial explorations in animal and human trials showed good results, with 3 weeks after clipping of the incised nipple not only showing scar repair of the nipple shape and structure, but also confirmed the recovery of sphincter function by Oddi sphincter manometry, the Oddi's sphincter basal pressure, contraction frequency and contraction amplitude were able to return to the pre-EST level. In summary, the investigators designed a single-center randomized controlled trial to explore and verify the clinical effect of ECPP on the prevention of recurrent bile duct stones within one year by comparing the incidence of recurrent bile duct stones within one year after EST surgery. By observing the changes of intestinal biliary reflux, biliary bacterial colonization, biliary microecology and bile metabolism after EST surgery, the pathogenesis of long-term complications such as recurrent bile duct stones after EST surgery was further sought.

Description:

Endoscopic retrograde cholangiopancreatography (ERCP) combined with endoscopic papillary sphinctomy (EST) is the preferred clinical treatment for common bile duct stones, and this minimally invasive treatment technique has been widely used in clinical practice for decades. However, even after successful stone removal by EST combined with various methods, the incidence of postoperative recurrent bile duct stones can still be as high as 9.8%~30% . The emergence of these long-term complications after EST surgery is currently thought to be related to the loss of Oddi sphincter function. EST sphincterotomy results in destruction of the Oddi sphincter structure, which in turn causes dysfunction and reflux of intestinal contents into the biliary tract (biliary reflux). In clinical practice, the investigators tried a new method to repair the Oddi sphincter, that is, after ERCP+EST stone removal, a metal clip was inserted into the endoscopic clamp through the duodenoscopy, and clamp precisely on both lateral edges of the nipple after incision. Initial explorations in animal and human trials showed good results, with 3 weeks after clipping of the incised nipple not only showing scar repair of the nipple shape and structure, but also confirmed the recovery of sphincter function by Oddi sphincter manometry, the Oddi's sphincter basal pressure, contraction frequency and contraction amplitude were able to return to the pre-EST level.

the investigators designed a single-center randomized controlled trial to explore and verify the clinical effect of ECPP on the prevention of recurrent bile duct stones within one year by comparing the incidence of recurrent bile duct stones within one year after EST surgery. This prospective study will be performed at 1 tertiary hospitals in China. The investigators will recruit patients according to admission criteria and exclusion criteria. The patients will be randomized (at a 1:1 ratio) to endoscopic papillary sphinctomy (EST) group (control group) and endoscopic nipple clipping (ECPP) group (experimental group). The control groups will be followed by routine EST stone removal, the patient's postoperative nipple is in a post-incision state; The experimental group underwent ECPP after EST. The primary endpoint is the incidence of recurrent bile duct stones. The secondary outcomes include the mortality of each group, adverse events and the rate of technical success.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: December 31, 2023
• Est. primary completion date: August 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Imaging confirms the presence of common bile duct stones.

• Common bile duct stones = 1.0 cm in length.

• Common bile duct inner diameter=1.2cm.

• The patient agrees to participate in the trial and signs the informed consent form.

Exclusion Criteria:

• Combined with coagulation dysfunction.

• heart, lung, kidney or other serious organic diseases.

• Patients with severe psychiatric illness.

• Previous papillary sphincterotomy.

• Patients who cannot cooperate with the completion of this study.

• Those with a life expectancy of less than 1 year and may not be able to complete follow-up.

Related Conditions & MeSH terms

• Sphincterotomy, Endoscopic

Intervention

Procedure:
• EST
Stones are taken by cutting the papillary sphincter
• ECPP
During ERCP, a generous biliary sphincterotomy (>1 cm) will be performed to facilitate large stone extraction by use of a lithotripsy basket and a stone extraction balloon. After all stone fragments were cleared from the bile duct, this group will undergo ECPP after EST. A single-pigtail biliary stent will be placed (suspended overlength biliary stent, 7F × 20 cm). Then the rotatable repeatable opening and closing of soft tissue clamps (referred to as harmony clips, Mico-Tech, ROCC-D-26-195) should be applied to extend the bile duct axially, linear clamp the incised duodenal papilla, taking care to avoid clamping the bile duct stent, and removing the bile duct stent 3 weeks after ECPP.

Locations

Country	Name	City	State
China	Peking University Third Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University Third Hospital

Country where clinical trial is conducted

China, 

References & Publications (12)

Afghani E, Lo SK, Covington PS, Cash BD, Pandol SJ. Sphincter of Oddi Function and Risk Factors for Dysfunction. Front Nutr. 2017 Jan 30;4:1. doi: 10.3389/fnut.2017.00001. eCollection 2017. — View Citation

Costamagna G, Tringali A, Shah SK, Mutignani M, Zuccala G, Perri V. Long-term follow-up of patients after endoscopic sphincterotomy for choledocholithiasis, and risk factors for recurrence. Endoscopy. 2002 Apr;34(4):273-9. doi: 10.1055/s-2002-23632. — View Citation

Kageoka M, Watanabe F, Maruyama Y, Nagata K, Ohata A, Noda Y, Miwa I, Ikeya K. Long-term prognosis of patients after endoscopic sphincterotomy for choledocholithiasis. Dig Endosc. 2009 Jul;21(3):170-5. doi: 10.1111/j.1443-1661.2009.00880.x. — View Citation

Mandryka Y, Klimczak J, Duszewski M, Kondras M, Modzelewski B. [Bile duct infections as a late complication after endoscopic sphincterotomy]. Pol Merkur Lekarski. 2006 Dec;21(126):525-7. Polish. — View Citation

Mortensen FV, Jepsen P, Tarone RE, Funch-Jensen P, Jensen LS, Sorensen HT. Endoscopic sphincterotomy and long-term risk of cholangiocarcinoma: a population-based follow-up study. J Natl Cancer Inst. 2008 May 21;100(10):745-50. doi: 10.1093/jnci/djn102. Epub 2008 May 13. — View Citation

Nzenza TC, Al-Habbal Y, Guerra GR, Manolas S, Yong T, McQuillan T. Recurrent common bile duct stones as a late complication of endoscopic sphincterotomy. BMC Gastroenterol. 2018 Mar 15;18(1):39. doi: 10.1186/s12876-018-0765-3. — View Citation

Stromberg C, Luo J, Enochsson L, Arnelo U, Nilsson M. Endoscopic sphincterotomy and risk of malignancy in the bile ducts, liver, and pancreas. Clin Gastroenterol Hepatol. 2008 Sep;6(9):1049-53. doi: 10.1016/j.cgh.2008.04.016. Epub 2008 Jun 30. — View Citation

Sugiyama M, Atomi Y. Risk factors predictive of late complications after endoscopic sphincterotomy for bile duct stones: long-term (more than 10 years) follow-up study. Am J Gastroenterol. 2002 Nov;97(11):2763-7. doi: 10.1111/j.1572-0241.2002.07019.x. — View Citation

Tanaka M, Takahata S, Konomi H, Matsunaga H, Yokohata K, Takeda T, Utsunomiya N, Ikeda S. Long-term consequence of endoscopic sphincterotomy for bile duct stones. Gastrointest Endosc. 1998 Nov;48(5):465-9. doi: 10.1016/s0016-5107(98)70086-0. — View Citation

Wang Y, Chang H, Zhang Y, Wang K, Zhang H, Yan X, Meng L, Yao W, Li K, Huang Y. Endoscopic endoclip papilloplasty preserves sphincter of oddi function. Eur J Clin Invest. 2021 Mar;51(3):e13408. doi: 10.1111/eci.13408. Epub 2020 Sep 22. — View Citation

Yang J, Jin H, Gu W, Zhang X, Zhang X. Determinants of long-term complications of endoscopic sphincterotomy are infections and high risk factors of bile duct and not sphincter of Oddi dysfunction. Eur J Gastroenterol Hepatol. 2015 Apr;27(4):412-8. doi: 10.1097/MEG.0000000000000295. — View Citation

Yasuda I, Fujita N, Maguchi H, Hasebe O, Igarashi Y, Murakami A, Mukai H, Fujii T, Yamao K, Maeshiro K, Tada T, Tsujino T, Komatsu Y. Long-term outcomes after endoscopic sphincterotomy versus endoscopic papillary balloon dilation for bile duct stones. Gastrointest Endosc. 2010 Dec;72(6):1185-91. doi: 10.1016/j.gie.2010.07.006. Epub 2010 Sep 25. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrent bile duct stones	The patient developed a recurrence of common bile duct stones within 1 year after surgery. Signs of recurrent bile duct stones include symptoms of cholangitis such as abdominal pain, fever, jaundice, or re-elevation of direct bilirubin/GGT/ALP or simple imaging of common bile duct stones.	12 months after ERCP
Secondary	Death or adverse events	The patient dies or develops postoperative complications of ERCP, stent displacement, detachment, etc., failure of ERCP.	12 months after ERCP