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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Pancreatic Fluid Collection, Pancreatitis, Pancreatic Pseudocyst

Intervention / Treatment
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* Procedure: Plastic stent
* Procedure: LAMS


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Plastic stent group<br>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<br>* 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.<br>|
| Active Comparator: LAMS group<br>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<br>* 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.<br>|

What is the study measuring?
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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 |
| --- | --- | --- |
| Number of participants with treatment-related adverse events | The adverse events are defined and graded by the ASGE lexicon guideline. | Five years | 
| Mortality | Mortality from any cause | 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 | 
| Duration of antibiotics administration | Total administration days of antibiotics | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endosonography, Drainage, Stents, Pancreatic Pseudocyst