Pinaverium Bromide Preventing Post Extracorporeal Shock Wave Lithotripsy Pancreatitis and Painful (PBPEP)

• Background:

• Chronic pancreatitis (CP) has a global incidence of 9.62/100,000, often complicated by pancreatic duct stones (90% of CP patients).
• p-ESWL is first-line for stones >5 mm but carries risks: pancreatitis (4.35%), abdominal pain (42.65%), and other complications (6.73% overall).
• Pinaverium bromide relaxes the sphincter of Oddi, reduce intestinal spasms and may mitigate post-ESWL complications.
• Objectives:

• Primary: Reduce post-p-ESWL pancreatitis incidence (per Atlanta 2012 criteria).
• Secondary: Decrease abdominal pain, other complications (bleeding, perforation, infection), and drug-related adverse events.
• Methods:

• Design: Single-center, randomized, double-blind, placebo-controlled.
• Sample size estimation This study used a comparative method of two sample rates in a superior efficacy clinical trial, with a unilateral test level of α=0.025 and a confidence level of 1- β=0.8. Based on the previous research on complications of lithotripsy conducted by our center, the incidence of abdominal pain in patients after the first P-ESWL surgery was approximately 42.65%. According to literature research results, pinaverium bromide can improve the relaxation of the Oddi's sphincter by 30-40%. Previous studies have shown that pinaverium bromide can control postoperative abdominal pain at around 18.75%. In this study, it is assumed that pinaverium bromide can reduce the incidence of abdominal pain after ESWL by 25%, from 42.65% to 17.65%, with a cut-off value of 10%, Nt：Nc=1：1. Based on Pearson chi square test, the required sample size was calculated to be 137 cases/group, totaling 274 cases.

Considering a rejection rate of 5%, the final required sample size is calculated to be 144 cases/group, totaling 288 cases.

• Intervention: Experimental Group Protocol

Preoperative Preparation:

Fasting: 12 hours before ESWL. Water restriction: 4 hours before surgery.

Medication:

Oral pinaverium bromide tablets (100mg tid) administered:

One day before surgery On the day of surgery One day post-surgery

Postoperative Monitoring:

Maintain fasting for 24 hours post-surgery.

Blood tests at 6h and 24h to assess:

Amylase, lipase, CBC, PCT, CRP Document abdominal pain scores. If abdominal pain worsens or recurs, perform imaging (e.g., abdominal CT). Control Group Protocol

Preoperative Preparation:

Identical to the experimental group (fasting 12h, water restriction 4h before ESWL).

Placebo Administration:

Oral placebo (2 tablets tid) given:

One day before surgery On the day of surgery One day post-surgery

Postoperative Monitoring:

Identical to the experimental group (fasting, blood tests, pain scoring, and imaging if needed).

Endpoint evaluation:

Patients will be closely monitored during and after surgery, with a mandatory hospital stay of at least 48 hours. Endpoint events, including ESWL-related complications (acute pancreatitis, stone street, bleeding, infection, perforation, or others), will be recorded.

Outcomes: Pancreatitis incidence, pain scores, complications, lab markers (amylase, CRP), and imaging.

Statistical Methods Principle: All data were analyzed based on the intention-to-treat (ITT) principle.

Continuous variables were compared using Student's t-test or Mann-Whitney U test, as appropriate.

Categorical variables were analyzed using the chi-square test or Fisher's exact test, depending on data distribution.

A P-value < 0.05 was considered statistically significant.

• Eligibility Criteria

Inclusion:

Age 18-85, CP with ≥5mm pancreatic duct stones (head predominance).

Exclusion:

• Requirement for repeat ESWL during the study period.
• Acute pancreatitis within 3 days prior to ESWL.
• Poor cardiopulmonary function with anesthesia intolerance.
• Severe liver disease (e.g., hepatic failure, liver abscess, cirrhosis, ascites).
• Anticoagulant therapy within 3 days or coagulopathy.
• Suspected or confirmed pancreatic tumor.
• Arteriosclerosis or abdominal aortic aneurysm obstructing shockwave transmission.
• Pregnancy or lactation.
• Allergy to pinaverium bromide
• Chronic pinaverium bromide use with discontinuation <3 days before ESWL
• Declined study participation

Termination Criteria:

• Inability to complete the ESWL procedure due to any reason after initiation.
• Non-compliance with the trial protocol by the patient.
• Voluntary withdrawal from the study. 5. Study Arms

• Experimental: Pinaverium bromide (100mg tid) pre-/post-ESWL.
• Control: Placebo controlled. 6. Primary Outcome Measures
• Incidence and severity of post-p-ESWL pancreatitis (Atlanta 2012 criteria). 7. Secondary Outcome Measures
• Abdominal pain (frequency, duration, scores).
• Other complications (infection, bleeding, stone street).
• Drug-related adverse events (e.g., diarrhea, rash). 8. Timeframe
• Enrollment: April 2025-April 2027.
• Completion: December 2027. 9. Contacts and Locations
• Principal Investigator: [Yanqing Li]
• Site: Qilu Hospital of Shandong University, China.

Inclusion criteria

• Gender is not limited, age range is 18-85 years old (inclusive);
• Perform P-ESWL treatment for painful chronic pancreatitis with positive pancreatic duct stones ≥ 5mm, mainly located in the head or body of the pancreas.

Exclusion criteria

• Requiring repeat ESWL during the study period.
• Acute pancreatitis within 3 days prior to ESWL.
• Severe cardiac/pulmonary dysfunction precluding anesthesia tolerance.
• Advanced liver disease (e.g., liver failure, cirrhosis, ascites, abscess).
• Anticoagulant use within 3 days or coagulopathy.
• Suspected or confirmed pancreatic malignancy.
• Arteriosclerosis or aortic aneurysm along shockwave transmission path.
• Pregnancy or lactation.
• Known allergy to pinaverium bromide.
• Chronic pinaverium bromide use with <3-day washout period.
• Declined participation.