WONDER-02 Trial: Plastic Stent vs. Lumen-apposing Metal Stent for Pancreatic Pseudocysts

WONDER-02: Plastic Stent vs. Lumen-apposing Metal Stent for Endoscopic Ultrasound-guided Drainage of Pancreatic Pseudocysts-a Multicentre Randomised Non-inferiority Trial

Endoscopic ultrasound (EUS)-guided transluminal drainage has become a first-line treatment modality for symptomatic pancreatic pseudocysts. Despite the increasing popularity of lumen-apposing metal stents (LAMSs), the use of a LAMS is limited by its high costs and specific adverse events compared to plastic stent placement. To date, there has been a paucity of data on the appropriate stent type in this setting. This trial aims to assess the non-inferiority of plastic stents to a LAMS for the initial EUS-guided drainage of pseudocysts.

Study Overview

• Status: Not yet recruiting
• Conditions: Pancreatitis; Pancreatic Pseudocyst; Pancreatic Fluid Collection
• Intervention / Treatment: Procedure: Plastic stent; Procedure: LAMS

Detailed Description

Pancreatic fluid collections (PFCs) develop as local complications of acute pancreatitis after four weeks of the disease onset. Pancreatic pseudocysts are a type of PFC, which is characterised by encapsulated non-necrotic contents. Pseudocysts occasionally become symptomatic (e.g., infection, GI symptoms), and given the high morbidity and mortality, it is mandatory to manage symptomatic pseudocysts appropriately to improve clinical outcomes of patients with acute pancreatitis overall. EUS-guided transluminal drainage has become a first-choice treatment option for symptomatic PFCs. In the setting of EUS-guided treatment of walled-off necrosis (WON, the other type of PFC), the potential benefits of LAMSs have been reported. Compared to plastic stents, LAMSs can serve as a transluminal port and thereby, facilitate the treatment of WON that often requires a long treatment duration with repeated interventions including direct endoscopic necrosectomy. With the increasing popularity and availability of LAMSs in interventional EUS overall, several retrospective studies have reported the feasibility of LAMS use for EUS-guided drainage of pancreatic pseudocysts.

While a LAMS may enhance the drainage efficiency of pseudocysts due to its large calibre, the benefits of this stent may be mitigated in pseudocysts that, by definition, contain non-necrotic liquid contents and can be managed without necrosectomy. Indeed, several retrospective comparative studies failed to demonstrate the superiority of plastic stents to a LAMS. In addition, the use of a LAMS has been limited by higher costs compared to plastic stents and potential specific adverse events (e.g., bleeding, buried stent). Studies suggest that a prolonged duration of LAMS placement (approximately ≥ 4 weeks) may predispose the patients to an elevated risk of adverse events associated with LAMSs. Therefore, patients requiring long-term drainage (e.g., cases with disconnected pancreatic duct syndrome) should be subjected to a reintervention in which a LAMS is replaced by a plastic stent. However, the technical success rate of the replacement has not been high. Given these lines of evidence, the investigators hypothesised that plastic stents might be non-inferior to a LAMS in terms of the potential of resolving a pseudocyst and associated symptoms.

To test the hypothesis, the investigators have planned a multicentre randomised controlled trial (RCT) to examine the non-inferiority of plastic stents to a LAMS as the initial stent for EUS-guided drainage of pancreatic pseudocysts in terms of the achievement of clinical treatment success (the resolution of a pseudocyst). Given the lower costs of plastic stents compared to a LAMS, the results would help not only establish a new treatment paradigm for pancreatic pseudocysts but also improve the cost-effectiveness of the resource-intensive treatment.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yousuke Nakai; Phone Number: +81-3-3815-5411; Email: ynakai-tky@umin.ac.jp
• Study Contact Backup: Name: Tomotaka Saito; Phone Number: +81-3-3815-5411; Email: tomsaito-gi@umin.ac.jp

Study Locations

• Japan
  • Aichi, Japan
    • Department of Gastroenterology, Aichi Medical University
    • Contact: Tadahisa Inoue
  • Bunkyō-Ku, Tokyo, Japan, 113-8655
    • Department of Gastroenterology, The University of Tokyo Hospital
    • Contact: Tomotaka Saito; Phone Number: +81-3-3815-5411; Email: tomsaito-gi@umin.ac.jp
    • Contact: Yousuke Nakai
  • Bunkyō-Ku, Tokyo, Japan
    • Department of Gastroenterology, Graduate School of Medicine, Juntendo University
    • Contact: Hiroyuki Isayama
    • Contact: Toshio Fujisawa
    • Sub-Investigator: Sho Takahashi
  • Chiba, Japan
    • Department of Gastroenterology, Graduate School of Medicine, Chiba University
    • Contact: Hiroshi Ohyama
    • Contact: Koji Takahashi
  • Fukuoka, Japan
    • Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University
    • Contact: Nao Fujimori
    • Contact: Kazuhide Matsumoto
  • Gifu, Japan
    • Department of Gastroenterology, Gifu Municipal Hospital
    • Contact: Keisuke Iwata
    • Contact: Mitsuru Okuno
  • Gifu, Japan
    • Department of Gastroenterology, Gifu Prefectural General Medical Center
    • Contact: Akinori Maruta
    • Contact: Kensaku Yoshida
  • Gifu, Japan
    • First Department of Internal Medicine, Gifu University Hospital
    • Contact: Takuji Iwashita
    • Contact: Shinya Uemura
  • Hyōgo, Japan
    • Division of Hepatobiliary and Pancreatic Diseases, Department of Gastroenterology, Hyogo Medical University
    • Contact: Hideyuki Shiomi
    • Contact: Ryota Nakano
  • Kagawa, Japan
    • Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University
    • Contact: Hideki Kamada
    • Contact: Ryota Nakabayashi
  • Kagoshima, Japan
    • Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences
    • Contact: Shinichi Hashimoto
    • Contact: Makoto Hinokuchi
  • Kamogawa, Japan
    • Department of Gastroenterology, Kameda Medical Center
    • Contact: Toshiyasu Shiratori
    • Contact: So Nakaji
  • Kanagawa, Japan
    • Department of Gastroenterology, St. Marianna University School of Medicine
    • Contact: Kazunari Nakahara
    • Contact: Yusuke Satta
  • Kanazawa, Japan
    • Department of Gastroenterological Endoscopy, Kanazawa Medical University
    • Contact: Tsuyoshi Mukai
  • Kawagoe, Japan
    • Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University
    • Contact: Saburo Matsubara
    • Contact: Kentaro Suda
  • Kawasaki, Japan
    • Department of Gastroenterology, Teikyo University Mizonokuchi Hospital
    • Contact: Shinpei Doi
    • Contact: Nobuhiro Katsukura
  • Kobe, Japan
    • Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine
    • Contact: Atsuhiro Masuda
    • Contact: Arata Sakai
    • Sub-Investigator: Masahiro Tsujimae
  • Mie, Japan
    • Department of Gastroenterology and Hepatology, Mie University Hospital
    • Contact: Reiko Yamada
    • Contact: Kenji Nose
  • Okayama, Japan
    • Department of Gastroenterology and Hepatology, Okayama University Hospital
    • Contact: Hironari Kato
    • Contact: Kazuyuki Matsumoto
    • Sub-Investigator: Ryosuke Sato
  • Osaka, Japan
    • 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University
    • Contact: Takeshi Ogura
    • Contact: Saori Ueno
  • Sapporo, Japan
    • Department of Gastroenterology and Hepatology, Hokkaido University Hospital
    • Contact: Masaki Kuwatani
    • Contact: Ryou Sugiura
  • Tokyo, Japan
    • Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine
    • Contact: Hirofumi Kogure
    • Contact: Kei Saito
  • Toyama, Japan
    • Third Department of Internal Medicine, University of Toyama
    • Contact: Ichiro Yasuda
    • Contact: Nobuhiko Hayashi
  • Wakayama, Japan
    • Department of Gastroenterology, Wakayama Medical University School of Medicine
    • Contact: Masayuki Kitano
    • Contact: Takashi Tamura
  • Yamanashi, Japan
    • Department of Gastroenterology, Yamanashi Prefectural Central Hospital
    • Contact: Sumio Hirose
  • Ōsaka, Japan
    • Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine
    • Contact: Mamoru Takenaka
    • Contact: Shunsuke Omoto

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with pancreatic pseudocyst(s) defined by the revised Atlanta classification
• The longest diameter of a targeted pseudocyst ≥ 5 cm
• Patients requiring drainage for symptoms associated with a pseudocyst (e.g., infection, gastrointestinal symptoms including abdominal pain, or jaundice)
• Patients aged 18 years or older
• Written informed consent obtained from patients or their representatives

Exclusion Criteria:

• A pseudocyst that is inaccessible via the EUS-guided approach
• A plastic or lumen-apposing metal stent in situ
• Coagulopathy (e.g., platelet count < 50,000/mm3 or prothrombin time international normalised ratio [PT-INR] >1.5)
• Users of antithrombotic agents that cannot be discontinued according to the Japan Gastroenterological Endoscopy Society [JGES] guidelines
• Patients who do not tolerate endoscopic procedures
• Pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Plastic stent group; In the plastic stent group, two (at least one) 7-Fr double pigtail stents will be placed. Following EUS-guided puncture of a pseudocyst, a guidewire will be coiled within the lesion, and another guidewire will be inserted alongside the prepositioned guidewire. The puncture tract will be dilated if needed.	Procedure: Plastic stent; EUS-guided drainage will be conducted under endosonographic and fluoroscopic guidance within 72 hours of the randomisation. A linear echoendoscope will be advanced to the stomach or duodenum with moderate sedation, and the targeted pseudocyst will be visualised and punctured under endosonographic guidance. In cases with an insufficient improvement in inflammatory indicators (i.e., body temperature, white blood cell count, and C-reactive protein), the investigators will perform additional interventions including the addition of or replacement with a plastic stent or LAMS and/or percutaneous drainage if needed. In the plastic stent group, two (at least one) 7-Fr double pigtail stents will be placed. Following EUS-guided puncture of a pseudocyst, a guidewire will be coiled within the lesion, and another guidewire will be inserted alongside the prepositioned guidewire. The puncture tract will be dilated if needed.
Active Comparator: LAMS group; In the LAMS group, a LAMS with electrocautery enhanced delivery will be placed (Hot AXIOS; Boston Scientific Japan, Tokyo, Japan). A guidewire or dilator will be used if needed.	Procedure: LAMS; EUS-guided drainage will be conducted under endosonographic and fluoroscopic guidance within 72 hours of the randomisation. A linear echoendoscope will be advanced to the stomach or duodenum with moderate sedation, and the targeted pseudocyst will be visualised and punctured under endosonographic guidance. In cases with an insufficient improvement in inflammatory indicators (i.e., body temperature, white blood cell count, and C-reactive protein), the investigators will perform additional interventions including the addition of or replacement with a plastic stent or LAMS and/or percutaneous drainage if needed. In the LAMS group, a LAMS with electrocautery enhanced delivery will be placed (Hot AXIOS; Boston Scientific Japan, Tokyo, Japan). A guidewire or dilator will be used if needed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical success within 180 days of randomisation	Clinical success is defined as 1) a decrease in the size of a targeted pancreatic pseudocyst to 2 cm or less and 2) an improvement of at least two out of the following inflammatory indicators: body temperature, white blood cell count, and C-reactive protein.	Six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Mortality from any cause	Five years
Duration of antibiotics administration	Total administration days of antibiotics	Six months
Number of participants with treatment-related adverse events	The adverse events are defined and graded by the ASGE lexicon guideline.	Five years
Technical success of the initial EUS-guided drainage	Technical success is defined as the successful placement of any stent in the targeted pseudocyst during the initial EUS-guided drainage.	One day
Time to clinical success	Time from randomization to clinical success	Six months
Incidence of biliary stricture	Biliary stricture due to a pseudocyst	Five years
Incidence of gastrointestinal stricture	Gastrointestinal obstruction due to a pseudocyst	Five years
Time requiring endoscopic drainage	Time requiring endoscopic drainage for a pseudocyst	Six months
Time requiring percutaneous drainage	Time requiring percutaneous drainage for a pseudocyst	Six months
Number of interventions	Total number of interventions needed for the treatment of a pseudocyst	Six months
Time of interventions	Total procedure time needed for the treatment of a pseudocyst	Six months
Length of the index hospitalisation	Total days of the index hospitalisation	Six months
Length of ICU stay during the index hospitalisation	Total ICU stay of the index hospitalisation	Six months
Costs of interventions	Total costs of treatment interventions	Six months
Costs of the index hospitalisation	Total costs of the index hospitalisation	Six months
Incidence of pseudocyst recurrence	Incidence of pseudocyst recurrence after clinical success	Five years
Time to recurrence of pancreatic pseudocyst	Time from clinical success to recurrence of pancreatic pseudocyst	Five years
Treatment duration of recurrent pancreatic pseudocyst	Total treatment days for recurrent pancreatic pseudocyst	Five years
New onset of pancreatic pseudocyst	Incidence of new-onset pancreatic pseudocyst	Five years
Treatment duration of new onset pancreatic pseudocyst	Total treatment days for new-onset pancreatic pseudocyst	Five years
Incidence of new onset diabetes	Incidence of new-onset diabetes mellitus	Five years
The presence of medications for pancreatic exocrine insufficiency	The start of medications for pancreatic exocrine insufficiency and the date	Five years
The presence of sarcopenia	The presence of sarcopenia and the date of diagnosis	Five years
Change in volume of pancreas	Change in volume of pancreas. Volume is evaluated by contrast-enhanced Computed Tomography (CT) using SYNAPSE VINCENT (FUJIFILM).	Five years
Success rate of surgical procedures	Success rate of surgeries associated with pancreatic pseudocyst	Six months
Operation time of surgical procedures	Total operation times	Six months
Incidence of new onset clinical symptoms of pancreatic exocrine insufficiency	New-onset clinical symptoms associated with pancreatic exocrine insufficiency, such as steatorrhea , constipation, diarrhea, maldigestion, flatulence, and tenesmus	Five years
Incidence of new pancreatic cancer	New-onset pancreatic cancer	Five years

Collaborators and Investigators

• Sponsor: Tokyo University
• Investigators: Principal Investigator: Yousuke Nakai, Department of Endoscopy and Endoscopic Surgery, Graduate School of Medicine, The University of Tokyo

Publications and helpful links

General Publications

• Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Tsiotos GG, Vege SS; Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013 Jan;62(1):102-11. doi: 10.1136/gutjnl-2012-302779. Epub 2012 Oct 25.

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): September 1, 2033

Study Registration Dates

• First Submitted: October 29, 2023
• First Submitted That Met QC Criteria: November 9, 2023
• First Posted (Actual): November 15, 2023

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 9, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Stents; Drainage; Pancreatic Pseudocyst; Endosonography
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Cysts; Pancreatic Diseases; Pancreatic Cyst; Pancreatitis; Pancreatic Pseudocyst
• Other Study ID Numbers: 2023002P

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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