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

Pancreatitis Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06133023
• Other study ID #: 2023002P
• Status: Not yet recruiting
• Phase: N/A
• Start date: November 2023
• Est. completion date: September 2033

Study information

• Verified date: November 2023
• Source: Tokyo University
• Contact: Yousuke Nakai
• Phone: +81-3-3815-5411
• Email: ynakai-tky[@]umin.ac.jp
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: September 2033
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pancreatic Pseudocyst
• Pancreatitis

Intervention

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.
• 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.

Locations

Country	Name	City	State
Japan	Department of Gastroenterology, Aichi Medical University	Aichi
Japan	Department of Gastroenterology, Graduate School of Medicine, Juntendo University	Bunkyo-Ku, Tokyo
Japan	Department of Gastroenterology, The University of Tokyo Hospital	Bunkyo-Ku, Tokyo
Japan	Department of Gastroenterology, Graduate School of Medicine, Chiba University	Chiba
Japan	Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University	Fukuoka
Japan	Department of Gastroenterology, Gifu Municipal Hospital	Gifu
Japan	Department of Gastroenterology, Gifu Prefectural General Medical Center	Gifu
Japan	First Department of Internal Medicine, Gifu University Hospital	Gifu
Japan	Division of Hepatobiliary and Pancreatic Diseases, Department of Gastroenterology, Hyogo Medical University	Hyogo
Japan	Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University	Kagawa
Japan	Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences	Kagoshima
Japan	Department of Gastroenterology, Kameda Medical Center	Kamogawa
Japan	Department of Gastroenterology, St. Marianna University School of Medicine	Kanagawa
Japan	Department of Gastroenterological Endoscopy, Kanazawa Medical University	Kanazawa
Japan	Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University	Kawagoe
Japan	Department of Gastroenterology, Teikyo University Mizonokuchi Hospital	Kawasaki
Japan	Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine	Kobe
Japan	Department of Gastroenterology and Hepatology, Mie University Hospital	Mie
Japan	Department of Gastroenterology and Hepatology, Okayama University Hospital	Okayama
Japan	2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University	Osaka
Japan	Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine	Osaka
Japan	Department of Gastroenterology and Hepatology, Hokkaido University Hospital	Sapporo
Japan	Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine	Tokyo
Japan	Third Department of Internal Medicine, University of Toyama	Toyama
Japan	Department of Gastroenterology, Wakayama Medical University School of Medicine	Wakayama
Japan	Department of Gastroenterology, Yamanashi Prefectural Central Hospital	Yamanashi

Sponsors (1)

Lead Sponsor	Collaborator
Tokyo University

Country where clinical trial is conducted

Japan, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of participants with treatment-related adverse events	The adverse events are defined and graded by the ASGE lexicon guideline.	Five years
Secondary	Mortality	Mortality from any cause	Five years
Secondary	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
Secondary	Time to clinical success	Time from randomization to clinical success	Six months
Secondary	Incidence of biliary stricture	Biliary stricture due to a pseudocyst	Five years
Secondary	Incidence of gastrointestinal stricture	Gastrointestinal obstruction due to a pseudocyst	Five years
Secondary	Time requiring endoscopic drainage	Time requiring endoscopic drainage for a pseudocyst	Six months
Secondary	Time requiring percutaneous drainage	Time requiring percutaneous drainage for a pseudocyst	Six months
Secondary	Number of interventions	Total number of interventions needed for the treatment of a pseudocyst	Six months
Secondary	Time of interventions	Total procedure time needed for the treatment of a pseudocyst	Six months
Secondary	Length of the index hospitalisation	Total days of the index hospitalisation	Six months
Secondary	Length of ICU stay during the index hospitalisation	Total ICU stay of the index hospitalisation	Six months
Secondary	Duration of antibiotics administration	Total administration days of antibiotics	Six months
Secondary	Costs of interventions	Total costs of treatment interventions	Six months
Secondary	Costs of the index hospitalisation	Total costs of the index hospitalisation	Six months
Secondary	Incidence of pseudocyst recurrence	Incidence of pseudocyst recurrence after clinical success	Five years
Secondary	Time to recurrence of pancreatic pseudocyst	Time from clinical success to recurrence of pancreatic pseudocyst	Five years
Secondary	Treatment duration of recurrent pancreatic pseudocyst	Total treatment days for recurrent pancreatic pseudocyst	Five years
Secondary	New onset of pancreatic pseudocyst	Incidence of new-onset pancreatic pseudocyst	Five years
Secondary	Treatment duration of new onset pancreatic pseudocyst	Total treatment days for new-onset pancreatic pseudocyst	Five years
Secondary	Incidence of new onset diabetes	Incidence of new-onset diabetes mellitus	Five years
Secondary	The presence of medications for pancreatic exocrine insufficiency	The start of medications for pancreatic exocrine insufficiency and the date	Five years
Secondary	The presence of sarcopenia	The presence of sarcopenia and the date of diagnosis	Five years
Secondary	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
Secondary	Success rate of surgical procedures	Success rate of surgeries associated with pancreatic pseudocyst	Six months
Secondary	Operation time of surgical procedures	Total operation times	Six months
Secondary	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
Secondary	Incidence of new pancreatic cancer	New-onset pancreatic cancer	Five years