Pinaverium Bromide in Post-cholecystectomy Sphincter of Oddi Dysfunction

NCT ID: NCT02833103

Last Updated: 2016-07-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 168 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-31
• Study Completion Date: 2018-02-28

Brief Summary

Sphincter of Oddi dysfunction (SOD) refers to biliary kinetic abnormality of the sphincter of Oddi (SO), often accompanied by pain, hepatic and pancreatic enzyme elevation, common bile duct (CBD) dilation or onset of pancreatitis. Pain caused by SOD affects the quality of life (QoL).The primary objective of this trial is to evaluate the efficacy of relieving abdominal pain of Pinaverium Bromide in medication therapy for patients with post-cholecystectomy SOD.

Detailed Description

1.1 Background (I)

1.1.1 10%~50% of the patients who previously underwent cholecystectomy experience recurrent abdominal pain with or without diarrhea, abdominal distention, enzymatic changes, etc., and sphincter of Oddi dysfunction (SOD) accounts for about 13% of such cases;

1.1.2 Sphincter of Oddi dysfunction (SOD):

• It refers to biliary kinetic abnormality of the sphincter of Oddi (SO), often accompanied by pain, hepatic and pancreatic enzyme elevation, common bile duct (CBD) dilation or onset of pancreatitis.
• Pain caused by SOD affects the quality of life (QoL).

1.1.3 The diagnosis of SOD is still being disputed, and there has been no optimal solution so far.

• The diagnosis of SOD is largely based on clinical judgment
• The gold standards ERCP and SOM are invasive diagnostic criteria

1.2 Background (II)

1.2.1 If biliary-type abdominal pain after cholecystectomy is considered as SOD, most of the patients are classified as SOD II and SOD III according to Rome III Criteria-modified.

Biliary SOD Type I: moderate or severe biliary-type abdominal pain; transient ALT / AST/ALP elevation > 2ULN; CBD dilation > 8mm as evidenced by ultrasound or other non-invasive examination Type II: biliary-type abdominal pain; One or two of above items Type III:only biliary-type abdominal pain

1.3 Background (III)

1.3.1 Treatment of SOD is being disputed: currently, the main method is to relax sphincter of Oddi (SO).

• Medications: antispasmodic drugs, nitrates, calcium ion antagonists, modulators of gastrointestinal (GI) motility
• EST(endoscopic sphincterotomy): postoperative complications and mortality

1.3.2 EST is not well effective in the treatment of SOD type II and type III, which are mostly caused by functional abnormalities

-ASGE guideline 2015 points out that EST is not recommended for patients with SOD type III. Endoscopic stents are not recommended, either.

1.3.3 Danshu Capsules: contains the active pharmaceutical ingredient (API) and has the effects of fighting infection, alleviating pain, promoting bile secretion and lifting muscle spasms; literature showed that Danshu Capsules effectively improved the symptoms of biliary disorders, such as pain, nausea and abdominal distension.

1.3.4 Pinaverium Bromide: able to improve the spasms of SO; literature showed that it treated biliary disorders effectively.·10%~50% of the patients who previously underwent cholecystectomy experience recurrent abdominal pain with or without diarrhea, abdominal distention, enzymatic changes, etc., and sphincter of Oddi dysfunction (SOD) accounts for about 13% of such cases.

Conditions

Sphincter of Oddi Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pinaverium Bromide group

Able to improve the spasms of SO; literature showed that it treated biliary disorders effectively.

Group Type: EXPERIMENTAL

Pinaverium Bromide

Intervention Type: DRUG

Pinaverium Bromide (100mg potid/day) for three months by oral

Danshu group

Contains the active pharmaceutical ingredient (API) and has the effects of fighting infection, alleviating pain, promoting bile secretion and lifting muscle spasms; literature showed that Danshu Capsules effectively improved the symptoms of biliary disorders, such as pain, nausea and abdominal distension.

Group Type: ACTIVE_COMPARATOR

Danshu Capsules

Intervention Type: DRUG

Danshu Capsules (0.9g potid/day) for three months by oral

Interventions

Danshu Capsules

Danshu Capsules (0.9g potid/day) for three months by oral

Intervention Type: DRUG

Pinaverium Bromide

Pinaverium Bromide (100mg potid/day) for three months by oral

Intervention Type: DRUG

Other Intervention Names

Danshu softgel Capsules; Dicetel

Eligibility Criteria

Inclusion Criteria

• Chief complaint of upper right abdominal pain following LC (within 2 weeks to 6 months) at a hospital visit, but not a pain caused by surgical incision, lasting 3 to 5 minutes each time, without a history of other biliary tract operation
• No presence of intestinal obstruction as evidenced by plain abdominal X-ray, with peptic ulcer and duodenal diverticulum ruled out through barium meal examination or gastroscopy
• No other obvious abnormalities as evidenced by abdominal ultrasound B and MRCP, except for bile duct dilation
• Patients with biliary-type sphincter of Oddi dysfunction (SOD) who are classified as SOD type II (biliary-type abdominal pain accompanied by hepatic enzyme elevation or common bile duct (CBD) dilation) and SOD type III (only biliary-type abdominal pain) according to Geenen-Hogan classification criteria

Exclusion Criteria

• Postoperative biliary calculi, benign biliary stenosis, bile duct infection, overlong residual cystic duct (> 0.5cm), biliary tumors, etc.
• Peptic ulcer, duodenal diverticulum
• Pancreatitis, pancreatic-type SOD
• Adhesive intestinal obstruction
• Postoperative irritable bowel syndrome (IBS)
• A history of abdominal operation or other surgery
• Pregnant and lactating women
• Use of other drugs from one week after LC to enrollment, including antispasmodic drugs, analgesics, choleretic agents, calcium ion antagonists and GI motility drugs
• A history of allergy to Pinaverium Bromide / Danshu Tablets

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Zhaohui Tang

the chief surgeon of the department of General Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhaohui Tang, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Xinhua Hospital,School of Medicine,Shanghai Jiao Tong University

Zhiwei Quan, MD,PhD

Role: STUDY_CHAIR

Xinhua Hospital,School of Medicine,Shanghai Jiao Tong University

Locations

Zhang Yong

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhaohui Tang, MD,PhD

Role: CONTACT

tangzhaohui@yahoo.com

+86 021 25078999-7905

Facility Contacts

Yong Zhang, MD,PhD

Role: primary

+86 21 25078999-7905

References

Cotton PB, Durkalski V, Romagnuolo J, Pauls Q, Fogel E, Tarnasky P, Aliperti G, Freeman M, Kozarek R, Jamidar P, Wilcox M, Serrano J, Brawman-Mintzer O, Elta G, Mauldin P, Thornhill A, Hawes R, Wood-Williams A, Orrell K, Drossman D, Robuck P. Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial. JAMA. 2014 May;311(20):2101-9. doi: 10.1001/jama.2014.5220.

Reference Type: BACKGROUND

PMID: 24867013 (View on PubMed)

Vitton V, Ezzedine S, Gonzalez JM, Gasmi M, Grimaud JC, Barthet M. Medical treatment for sphincter of oddi dysfunction: can it replace endoscopic sphincterotomy? World J Gastroenterol. 2012 Apr 14;18(14):1610-5. doi: 10.3748/wjg.v18.i14.1610.

Reference Type: BACKGROUND

PMID: 22529689 (View on PubMed)

Okoro N, Patel A, Goldstein M, Narahari N, Cai Q. Ursodeoxycholic acid treatment for patients with postcholecystectomy pain and bile microlithiasis. Gastrointest Endosc. 2008 Jul;68(1):69-74. doi: 10.1016/j.gie.2007.09.046.

Reference Type: BACKGROUND

PMID: 18577477 (View on PubMed)

Kalaitzakis E, Ambrose T, Phillips-Hughes J, Collier J, Chapman RW. Management of patients with biliary sphincter of Oddi disorder without sphincter of Oddi manometry. BMC Gastroenterol. 2010 Oct 22;10:124. doi: 10.1186/1471-230X-10-124.

Reference Type: BACKGROUND

PMID: 20969779 (View on PubMed)

Behar J, Corazziari E, Guelrud M, Hogan W, Sherman S, Toouli J. Functional gallbladder and sphincter of oddi disorders. Gastroenterology. 2006 Apr;130(5):1498-509. doi: 10.1053/j.gastro.2005.11.063.

Reference Type: BACKGROUND

PMID: 16678563 (View on PubMed)

Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology. 2006 Apr;130(5):1377-90. doi: 10.1053/j.gastro.2006.03.008. No abstract available.

Reference Type: BACKGROUND

PMID: 16678553 (View on PubMed)

Hernando N, Gisler SM, Reining SC, Deliot N, Capuano P, Biber J, Murer H. NaPi-IIa interacting proteins and regulation of renal reabsorption of phosphate. Urol Res. 2010 Aug;38(4):271-6. doi: 10.1007/s00240-010-0304-3. Epub 2010 Jul 28.

Reference Type: BACKGROUND

PMID: 20665015 (View on PubMed)

Other Identifiers

XH-16-015

Identifier Type: -

Identifier Source: org_study_id