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

Official title

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

Overview

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.

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.

Interventions

• 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 interve
• 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 interve

Primary outcome measures

• Clinical success within 180 days of randomisation [Time frame: Six months]

Secondary outcome measures (12)

• Number of participants with treatment-related adverse events [Time frame: Five years]
• Mortality [Time frame: Five years]
• Technical success of the initial EUS-guided drainage [Time frame: One day]
• Time to clinical success [Time frame: Six months]
• Incidence of biliary stricture [Time frame: Five years]
• Incidence of gastrointestinal stricture [Time frame: Five years]
• Time requiring endoscopic drainage [Time frame: Six months]
• Time requiring percutaneous drainage [Time frame: Six months]
• Number of interventions [Time frame: Six months]
• Time of interventions [Time frame: Six months]
• Length of the index hospitalisation [Time frame: Six months]
• Length of ICU stay during the index hospitalisation [Time frame: Six months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Japan · 26 centers

• Department of Gastroenterology, Aichi Medical University — Aichi
• Department of Gastroenterology, The University of Tokyo Hospital — Bunkyō-Ku, Tokyo
• Department of Gastroenterology, Graduate School of Medicine, Juntendo University — Bunkyō-Ku, Tokyo
• Department of Gastroenterology, Graduate School of Medicine, Chiba University — Chiba
• Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyu — Fukuoka
• Department of Gastroenterology, Gifu Municipal Hospital — Gifu
• Department of Gastroenterology, Gifu Prefectural General Medical Center — Gifu
• First Department of Internal Medicine, Gifu University Hospital — Gifu
• … and 18 more centers

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. PMID 23100216
• Saito T, Takenaka M, Kuwatani M, Doi S, Ohyama H, Fujisawa T, Masuda A, Iwashita T, Shiomi H, Hayashi N, Iwata K, Maruta A, Mukai T, Matsubara S, Hamada T, Inoue T, Matsumoto K, Hirose S, Fujimori N, Kashiwabara K, Kamada H, Hashimoto S, Shiratori T, Yamada R, Kogure H, Nakahara K, Ogura T, Kitano M, Yasuda I, Isayama H, Nakai Y; WONDERFUL study group in Japan and collaborators. WONDER-02: plastic PMID 39182137

Identifiers

NCT: NCT06133023 · 2023002P

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗