Clinical trial NCT02833103: Pinaverium Bromide in Post-cholecystectomy Sphincter of Oddi Dysfunction
Official title: Application of Pinaverium Bromide in the Treatment of Patients With Post-cholecystectomy Sphincter of Oddi Dysfunction (SOD): A Randomized, Controlled and Multicenter Clinical Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Sphincter of Oddi Dysfunction
Keywords: Pinaverium Bromide
cholecystectomy
Sphincter of Oddi Dysfunction
Lead sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2016-07-14
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Efficacy Evaluation of Reduction in Abdominal Pain Scores，Change From Baseline to 3 Months After Medication
timeFrame: Change From Baseline to 3 Months After Medication
Secondary outcomes:
measure: Changes in the Common Bile Duct (CBD) Diameter Measured by Ultrasound B Once a Month
timeFrame: Once a Month, Four Times Totally (baseline / 4w after treatment / 8w after treatment / 12w after treatment)
measure: Efficacy of Lowering Liver Enzymes as Assessed by Laboratory Test Once a Month
timeFrame: Once a Month, Four Times Totally (baseline / 4w after treatment / 8w after treatment / 12w after treatment)
measure: Number of Participants With Treatment-Related Diarrhea,Change From Baseline to 3 Months After Medication
timeFrame: From Baseline to 3 Months After Medication
Other outcomes:
measure: Number of Participants With Treatment-Related Adverse Events as Assessed by Researchers or Doctors Through Study Completion
timeFrame: Through Study Completion, An Average of 1 Year
Locations:
city: Shanghai
country: China
facility: Zhang Yong
state: Shanghai
Study officials:
affiliation: Xinhua Hospital,School of Medicine,Shanghai Jiao Tong University
name: Zhaohui Tang, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Xinhua Hospital,School of Medicine,Shanghai Jiao Tong University
name: Zhiwei Quan, MD,PhD
role: STUDY_CHAIR
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