Clinical trial NCT06133023: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Pancreatic Fluid Collection
Pancreatitis
Pancreatic Pseudocyst
Keywords: Endosonography
Drainage
Stents
Pancreatic Pseudocyst
Lead sponsor: Tokyo University
Sponsor class: OTHER
First posted: 2023-11-15
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: Clinical success within 180 days of randomisation
timeFrame: Six months
Secondary outcomes:
measure: Number of participants with treatment-related adverse events
timeFrame: Five years
measure: Mortality
timeFrame: Five years
measure: Technical success of the initial EUS-guided drainage
timeFrame: One day
measure: Time to clinical success
timeFrame: Six months
measure: Incidence of biliary stricture
timeFrame: Five years
measure: Incidence of gastrointestinal stricture
timeFrame: Five years
measure: Time requiring endoscopic drainage
timeFrame: Six months
measure: Time requiring percutaneous drainage
timeFrame: Six months
measure: Number of interventions
timeFrame: Six months
measure: Time of interventions
timeFrame: Six months
measure: Length of the index hospitalisation
timeFrame: Six months
measure: Length of ICU stay during the index hospitalisation
timeFrame: Six months
measure: Duration of antibiotics administration
timeFrame: Six months
measure: Costs of interventions
timeFrame: Six months
measure: Costs of the index hospitalisation
timeFrame: Six months
measure: Incidence of pseudocyst recurrence
timeFrame: Five years
measure: Time to recurrence of pancreatic pseudocyst
timeFrame: Five years
measure: Treatment duration of recurrent pancreatic pseudocyst
timeFrame: Five years
measure: New onset of pancreatic pseudocyst
timeFrame: Five years
measure: Treatment duration of new onset pancreatic pseudocyst
timeFrame: Five years
measure: Incidence of new onset diabetes
timeFrame: Five years
measure: The presence of medications for pancreatic exocrine insufficiency
timeFrame: Five years
measure: The presence of sarcopenia
timeFrame: Five years
measure: Change in volume of pancreas
timeFrame: Five years
measure: Success rate of surgical procedures
timeFrame: Six months
measure: Operation time of surgical procedures
timeFrame: Six months
measure: Incidence of new onset clinical symptoms of pancreatic exocrine insufficiency
timeFrame: Five years
measure: Incidence of new pancreatic cancer
timeFrame: Five years
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Department of Gastroenterology, Aichi Medical University
city: Bunkyō-Ku, Tokyo
country: Japan
facility: Department of Gastroenterology, The University of Tokyo Hospital
city: Bunkyō-Ku, Tokyo
country: Japan
facility: Department of Gastroenterology, Graduate School of Medicine, Juntendo University
city: Chiba
country: Japan
facility: Department of Gastroenterology, Graduate School of Medicine, Chiba University
city: Fukuoka
country: Japan
facility: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University
city: Gifu
country: Japan
facility: Department of Gastroenterology, Gifu Municipal Hospital
city: Gifu
country: Japan
facility: Department of Gastroenterology, Gifu Prefectural General Medical Center
city: Gifu
country: Japan
facility: First Department of Internal Medicine, Gifu University Hospital
city: Hyōgo
country: Japan
facility: Division of Hepatobiliary and Pancreatic Diseases, Department of Gastroenterology, Hyogo Medical University
city: Kagawa
country: Japan
facility: Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University
city: Kagoshima
country: Japan
facility: Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences
city: Kamogawa
country: Japan
facility: Department of Gastroenterology, Kameda Medical Center
city: Kanagawa
country: Japan
facility: Department of Gastroenterology, St. Marianna University School of Medicine
city: Kanazawa
country: Japan
facility: Department of Gastroenterological Endoscopy, Kanazawa Medical University
city: Kawagoe
country: Japan
facility: Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University
city: Kawasaki
country: Japan
facility: Department of Gastroenterology, Teikyo University Mizonokuchi Hospital
city: Kobe
country: Japan
facility: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine
city: Mie
country: Japan
facility: Department of Gastroenterology and Hepatology, Mie University Hospital
city: Okayama
country: Japan
facility: Department of Gastroenterology and Hepatology, Okayama University Hospital
city: Osaka
country: Japan
facility: 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University
city: Sapporo
country: Japan
facility: Department of Gastroenterology and Hepatology, Hokkaido University Hospital
city: Tokyo
country: Japan
facility: Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine
city: Toyama
country: Japan
facility: Third Department of Internal Medicine, University of Toyama
city: Wakayama
country: Japan
facility: Department of Gastroenterology, Wakayama Medical University School of Medicine
city: Yamanashi
country: Japan
facility: Department of Gastroenterology, Yamanashi Prefectural Central Hospital
city: Ōsaka
country: Japan
facility: Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine
Study officials:
affiliation: Department of Endoscopy and Endoscopic Surgery, Graduate School of Medicine, The University of Tokyo
name: Yousuke Nakai
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.