Long-duration EPBD vs EST for Removal of Biliary Stones

Long-duration (3 Minutes) Endoscopic Papillary Balloon Dilation Versus Endoscopic Sphincterotomy in Patients With a Naive Major Papilla and Small- to Medium Sized Biliary Stones: Multicenter, Randomized, Controlled Trial

Although EPBD has a lower risk of post-ERCP bleeding and long-term complications than EST and is easier to perform in altered/difficult anatomy, EPBD is reserved for patients with bleeding diathesis by current consensus because some studies reported a higher risk of pancreatitis. However, recent meta-analyses indicate that short EPBD duration increases the risk of post-ERCP pancreatitis, and EPBD with adequate duration has a similar pancreatitis risk and a lower overall complication rate compared with EST for choledocholithiasis.

Therefore, this study aim to compare long-duration EPBD vs EST in the treatment of extrahepatic biliary stones.

Study Overview

• Status: Unknown
• Conditions: Cholangiopancreatography, Endoscopic Retrograde
• Intervention / Treatment: Procedure: long duration EPBD; Procedure: EST

Detailed Description

Gallstones occur in 10%-15% of adults in the United States and are the most common and costly digestive disorder. Concomitant bile duct stones occur in up to 15% of persons with symptomatic gallstones. Endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy is the standard treatment for removal choledocholithiasis. The biliary sphincter is permanently ablated by sphincterotomy. Enteric-biliary reflux occurs with bacterial colonization, increased bile lithogenicity, contamination with cytotoxins, and chronic inflammation of the biliary system. Endoscopic papillary balloon dilation (EPBD) has become an option for removal of stones 1 cm or smaller in size. Advantages of EPBD over EST include a decreased risk of post-ERCP bleeding as well as a decreased risk of stone recurrence and cholangitis. Although a short dilation duration (≤1 minute) was previously advocated, a study that performed EPBD for 1 minute observed a 15.4% risk of post-ERCP pancreatitis with 2 cases of mortality. European Society of Gastrointestinal Endoscopy guideline recommends that the duration of EPBD should exceed 2 minutes because long-duration EPBD (>1 minute) is preferred over short-duration EPBD (≤1 minute) with better outcomes. A meta-analysis of RCTs showed that the duration of EPBD is inversely associated with the risk of PEP. Previous RCTs comparing outcome between EPBD and EST used short EPBD duration between 25 seconds and 1 minute, and there has been no comparison of outcome between EST and long-duration EPBD. The aim of this study was to compare the early and long term outcomes of patients treated with long duration balloon dilation or sphincterotomy for extraction of bile duct stones in a randomized, multicenter fashion involving a broad spectrum of practices.

• Study Type: Interventional
• Enrollment (Anticipated): 358
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of
    • Recruiting
    • Inje University, Haeundae paik hospital
    • Contact: Joon Hyuck Choi, MD; Email: cladius2@naver.com
  • Daejeon, Korea, Republic of
    • Recruiting
    • St. Mary's Hospital, The Catholic University of Korea,
    • Contact: Won Seok Park, MD; Email: mdonekr@naver.com
    • Contact: Kyu-Hyun Paik, MD
  • Chungcheongnam-do
    • Cheonan, Chungcheongnam-do, Korea, Republic of, 330-715
      • Recruiting
      • Dankook University College of Medicine
      • Contact: Jun Ho Choi, MD, PhD; Phone Number: 82-41-550-7631; Email: mdcjh78@gmail.com
      • Contact: Se Weon Kim, MD; Phone Number: 82-41-550-6694; Email: intern41@dkuh.co.kr
  • Jeollabukdo
    • Iksan, Jeollabukdo, Korea, Republic of
      • Recruiting
      • Wonkwang University
      • Contact: Hyung Ku Chon, MD; Phone Number: 82-63-859-2564; Email: menzo@jbnu.ac.kr
      • Contact: Tae Hyeon Kim, MD, PhD; Email: kth@wonkwang.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Consecutive patients were invited to participate by the investigators or research staff if they were at least 18 years old,
• patients who had known or suspected choledocholithiasis

Exclusion Criteria:

• active acute pancreatitis
• septic shock,
• coagulopathy (international normalized ratio >1.2, partial thromboplastic time greater than twice that of control),
• platelet count <50,000 x 103/uL,
• anticoagulation therapy within 48 hours of the procedure,
• stone diameter > 8 mm,
• bile duct diameter >15 mm, prior sphincterotomy,
• need for precut sphincterotomy for biliary access,
• biliary stricture,
• Billroth II or Roux-en-Y anatomy,
• periampullary malignancies,
• primary sclerosing cholangitis, pregnancy,
• and inability to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: long duration EPBD group; Balloon dilation was performed using wire-guided hydrostatic balloon catheters. An 8-mm dilatation balloon was used for EPBD. Balloons were gradually inflated to maximum pressure for 3 minute, and complete inflation was verified by fluoroscopy. Stones were removed by standard techniques, including balloon or basket catheters.	Procedure: long duration EPBD; An 8-mm dilatation balloon was used for EPBD. Balloons were gradually inflated to maximum pressure for 3 minute, and complete inflation was verified by fluoroscopy.; Procedure: EST; After deep cannulation was achieved, a complete sphincterotomy was performed with a 25-mm pull-type sphincterotome (Clever Cut 3; KD-V411M, Olympus, Tokyo, Japan) and the sphincter was divided up to the transverse duodenal fold.
Active Comparator: endoscopic sphincterotomy (EST) group; After deep cannulation was achieved, a complete sphincterotomy was performed with a 25-mm pull-type sphincterotome (Clever Cut 3; KD-V411M, Olympus, Tokyo, Japan) and the sphincter was divided up to the transverse duodenal fold. A complete sphincterotomy was defined by the free passage of a fully bowed sphincterotome and the presence of spontaneous bile drainage. A complete sphincterotomy was defined by the free passage of a fully bowed sphincterotome and the presence of spontaneous bile drainage.	Procedure: long duration EPBD; An 8-mm dilatation balloon was used for EPBD. Balloons were gradually inflated to maximum pressure for 3 minute, and complete inflation was verified by fluoroscopy.; Procedure: EST; After deep cannulation was achieved, a complete sphincterotomy was performed with a 25-mm pull-type sphincterotome (Clever Cut 3; KD-V411M, Olympus, Tokyo, Japan) and the sphincter was divided up to the transverse duodenal fold.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rate of adverse event	Number of participants with treatment-related adverse events	up to 1 month after ERCP

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the stone clearance rate at the index ERCP	complete extraction of choledocholithiasis of all stones, fragments, and sludge at the initial procedure	during ERCP
direct cost	The direct cost included the total cost for the entire admission, which comprised costs of hospital stay, performed procedures, and management of complications	within 30 day after ERCP
recurrence of choledocholithiasis	recurrent choledocholithiasis or acute cholangitis either with or without bile duct stones, and overall hepatobiliary complications	more than 3 year follow-up
adverse event (pancreatitis)	rate of pancreatitis	up to 1 month after ERCP
adverse event (bleeding)	rate of bleeding	up to 1 month after ERCP
adverse event (cholangitis)	rate of cholangitis	up to 1 month after ERCP

Collaborators and Investigators

• Sponsor: Dankook University
• Collaborators: Inje University; The Catholic University of Korea; Wonkwang University
• Investigators: Principal Investigator: Jun Ho Choi, MD, PhD, Dankook University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2018
• Primary Completion (Anticipated): May 1, 2019
• Study Completion (Anticipated): August 1, 2021

Study Registration Dates

• First Submitted: April 5, 2018
• First Submitted That Met QC Criteria: September 21, 2018
• First Posted (Actual): September 25, 2018

Study Record Updates

• Last Update Posted (Actual): October 1, 2018
• Last Update Submitted That Met QC Criteria: September 27, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Cholangiopancreatography, Endoscopic Retrograde
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathological Conditions, Anatomical; Gallbladder Diseases; Biliary Tract Diseases; Calculi; Gallstones; Cholelithiasis; Cholecystolithiasis
• Other Study ID Numbers: 2018-03-009

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No