WONDER-02 Trial: Plastic Stent vs. Lumen-apposing Metal Stent for Pancreatic Pseudocysts
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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 Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Clinical success within 180 days of randomisation [Six months]
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.
Secondary Outcome Measures
- Number of participants with treatment-related adverse events [Five years]
The adverse events are defined and graded by the ASGE lexicon guideline.
- Mortality [Five years]
Mortality from any cause
- Technical success of the initial EUS-guided drainage [One day]
Technical success is defined as the successful placement of any stent in the targeted pseudocyst during the initial EUS-guided drainage.
- Time to clinical success [Six months]
Time from randomization to clinical success
- Incidence of biliary stricture [Five years]
Biliary stricture due to a pseudocyst
- Incidence of gastrointestinal stricture [Five years]
Gastrointestinal obstruction due to a pseudocyst
- Time requiring endoscopic drainage [Six months]
Time requiring endoscopic drainage for a pseudocyst
- Time requiring percutaneous drainage [Six months]
Time requiring percutaneous drainage for a pseudocyst
- Number of interventions [Six months]
Total number of interventions needed for the treatment of a pseudocyst
- Time of interventions [Six months]
Total procedure time needed for the treatment of a pseudocyst
- Length of the index hospitalisation [Six months]
Total days of the index hospitalisation
- Length of ICU stay during the index hospitalisation [Six months]
Total ICU stay of the index hospitalisation
- Duration of antibiotics administration [Six months]
Total administration days of antibiotics
- Costs of interventions [Six months]
Total costs of treatment interventions
- Costs of the index hospitalisation [Six months]
Total costs of the index hospitalisation
- Incidence of pseudocyst recurrence [Five years]
Incidence of pseudocyst recurrence after clinical success
- Time to recurrence of pancreatic pseudocyst [Five years]
Time from clinical success to recurrence of pancreatic pseudocyst
- Treatment duration of recurrent pancreatic pseudocyst [Five years]
Total treatment days for recurrent pancreatic pseudocyst
- New onset of pancreatic pseudocyst [Five years]
Incidence of new-onset pancreatic pseudocyst
- Treatment duration of new onset pancreatic pseudocyst [Five years]
Total treatment days for new-onset pancreatic pseudocyst
- Incidence of new onset diabetes [Five years]
Incidence of new-onset diabetes mellitus
- The presence of medications for pancreatic exocrine insufficiency [Five years]
The start of medications for pancreatic exocrine insufficiency and the date
- The presence of sarcopenia [Five years]
The presence of sarcopenia and the date of diagnosis
- Change in volume of pancreas [Five years]
Change in volume of pancreas. Volume is evaluated by contrast-enhanced Computed Tomography (CT) using SYNAPSE VINCENT (FUJIFILM).
- Success rate of surgical procedures [Six months]
Success rate of surgeries associated with pancreatic pseudocyst
- Operation time of surgical procedures [Six months]
Total operation times
- Incidence of new onset clinical symptoms of pancreatic exocrine insufficiency [Five years]
New-onset clinical symptoms associated with pancreatic exocrine insufficiency, such as steatorrhea , constipation, diarrhea, maldigestion, flatulence, and tenesmus
- Incidence of new pancreatic cancer [Five years]
New-onset pancreatic cancer
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients with pancreatic pseudocyst(s) defined by the revised Atlanta classification
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The longest diameter of a targeted pseudocyst ≥ 5 cm
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Patients requiring drainage for symptoms associated with a pseudocyst (e.g., infection, gastrointestinal symptoms including abdominal pain, or jaundice)
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Patients aged 18 years or older
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Written informed consent obtained from patients or their representatives
Exclusion Criteria:
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A pseudocyst that is inaccessible via the EUS-guided approach
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A plastic or lumen-apposing metal stent in situ
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Coagulopathy (e.g., platelet count < 50,000/mm3 or prothrombin time international normalised ratio [PT-INR] >1.5)
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Users of antithrombotic agents that cannot be discontinued according to the Japan Gastroenterological Endoscopy Society [JGES] guidelines
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Patients who do not tolerate endoscopic procedures
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Pregnant women
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Gastroenterology, Aichi Medical University | Aichi | Japan | ||
| 2 | Department of Gastroenterology, The University of Tokyo Hospital | Bunkyō-Ku, Tokyo | Japan | 113-8655 | |
| 3 | Department of Gastroenterology, Graduate School of Medicine, Juntendo University | Bunkyō-Ku, Tokyo | Japan | ||
| 4 | Department of Gastroenterology, Graduate School of Medicine, Chiba University | Chiba | Japan | ||
| 5 | Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University | Fukuoka | Japan | ||
| 6 | Department of Gastroenterology, Gifu Municipal Hospital | Gifu | Japan | ||
| 7 | Department of Gastroenterology, Gifu Prefectural General Medical Center | Gifu | Japan | ||
| 8 | First Department of Internal Medicine, Gifu University Hospital | Gifu | Japan | ||
| 9 | Division of Hepatobiliary and Pancreatic Diseases, Department of Gastroenterology, Hyogo Medical University | Hyōgo | Japan | ||
| 10 | Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University | Kagawa | Japan | ||
| 11 | Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences | Kagoshima | Japan | ||
| 12 | Department of Gastroenterology, Kameda Medical Center | Kamogawa | Japan | ||
| 13 | Department of Gastroenterology, St. Marianna University School of Medicine | Kanagawa | Japan | ||
| 14 | Department of Gastroenterological Endoscopy, Kanazawa Medical University | Kanazawa | Japan | ||
| 15 | Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University | Kawagoe | Japan | ||
| 16 | Department of Gastroenterology, Teikyo University Mizonokuchi Hospital | Kawasaki | Japan | ||
| 17 | Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine | Kobe | Japan | ||
| 18 | Department of Gastroenterology and Hepatology, Mie University Hospital | Mie | Japan | ||
| 19 | Department of Gastroenterology and Hepatology, Okayama University Hospital | Okayama | Japan | ||
| 20 | 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University | Osaka | Japan | ||
| 21 | Department of Gastroenterology and Hepatology, Hokkaido University Hospital | Sapporo | Japan | ||
| 22 | Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine | Tokyo | Japan | ||
| 23 | Third Department of Internal Medicine, University of Toyama | Toyama | Japan | ||
| 24 | Department of Gastroenterology, Wakayama Medical University School of Medicine | Wakayama | Japan | ||
| 25 | Department of Gastroenterology, Yamanashi Prefectural Central Hospital | Yamanashi | Japan | ||
| 26 | Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine | Ōsaka | Japan |
Sponsors and Collaborators
- Tokyo University
Investigators
- Principal Investigator: Yousuke Nakai, Department of Endoscopy and Endoscopic Surgery, Graduate School of Medicine, The University of Tokyo
Study Documents (Full-Text)
None provided.More Information
Publications
- 2023002P