Clinical trial NCT05451901: Immediate Necrosectomy vs. Step-up Approach for Walled-off Necrosis
Official title: Immediate Necrosectomy vs. Step-up Approach After EUS-guided Drainage of Walled-off Necrosis: a Multicenter Randomized Controlled Trial (WONDER-01)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Pancreatic Fluid Collection
Walled-off Necrosis
Pancreatitis, Acute Necrotizing
Pancreatic Pseudocyst
Keywords: Endosonography
Drainage
Stents
Endoscopic necrosectomy
Step-up approach
Lead sponsor: Tokyo University
Sponsor class: OTHER
First posted: 2022-07-11
Enrollment: 70
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: Walled-off necrosis (WON) is a pancreatic fluid collection, which contains necrotic tissue after four weeks of the onset of acute pancreatitis. Interventions are required to manage patients with infected WON, for which endoscopic ultrasonography (EUS)-guided drainage has become a first-line treatment modality. For patients who are refractory to EUS-guided drainage, the step-up treatment including endoscopic necrosectomy (EN) and/or additional drainage is considered to subside the infection. Recent evidence suggests that EN immediately after EUS-guided drainage may shorten treatment duration without increasing adverse events. In this randomized trial, the investigators will compare treatment duration between EN immediately after EUS-guided drainage versus the step-up approach in patients with symptomatic WON.

Detailed description: Pancreatic fluid collection is a late complication of severe acute pancreatitis. According to the revised Atlanta classification, walled-off necrosis (WON) is defined as an encapsulated collection of necrotic tissue that is observed after four weeks of the onset of acute pancreatitis. Infected WON is associated with high morbidity and mortality; therefore, an appropriate treatment, including antibiotics and drainage, is mandatory. With the development of endoscopic equipment, endoscopic ultrasonography (EUS)-guided drainage has become a first-line treatment modality for infected WON. For patients who are refractory to EUS-guided drainage, endoscopic necrosectomy (EN) is a treatment option to facilitate direct removal of infected necrotic tissue within the WON. However, due to potentially lethal adverse events of EN, such as bleeding, perforation, and peritonitis, EN is usually withheld for several days after EUS-guided drainage. This strategy is known as "the step-up approach." Recently, with the accumulated evidence supporting the safety of EN, especially with the use of a dedicated lumen-apposing metal stent, it has been reported that EN immediately after EUS-guided drainage can shorten the treatment duration without increasing adverse events. Given these lines of evidence, the investigators hypothesized that immediate EN following EUS-guided drainage of WON might shorten time to clinical success compared to the step-up approach. To examine this hypothesis, the investigators planned to conduct a multicenter randomized controlled trial comparing treatment duration between EN immediately after EUS-guided drainage versus the step-up approach in patients with symptomatic WON.

Eligibility criteria: Inclusion Criteria:

* Patients with WON defined according to the revised Atlanta classification
* The longest diameter of WON is 4 cm or larger
* Patients with at least one out of the following conditions; signs of infection, gastrointestinal symptoms, abdominal symptoms, obstructive jaundice
* Patients who need drainage for WON
* Age of 18 years or older
* Patients or their representatives provide informed consent
* Patients who visit or are hospitalized at the participating institutions

Exclusion Criteria:

* WON inaccessible by EUS-guided approach
* AXIOS stent has already been placed into the WON prior to the enrollment
* Severe coagulopathy; Platelet count \< 50,000/mm3 or prothrombin time international normalized ratio (PT-INR) \>1.5
* Patients on antithrombotic agents which cannot be managed according to the "guideline for gastroenterological endoscopy in patients undergoing antithrombotic treatment (Dig Endosc. 2014 Jan;26(1):1-14.)"
* Patients who cannot tolerate endoscopic procedures
* Pregnant women
* Patients considered inappropriate for inclusion by investigators

Primary outcomes:
measure: Time to clinical success from randomization
timeFrame: Six months
Secondary outcomes:
measure: Adverse events
timeFrame: Five years
measure: Mortality
timeFrame: Five years
measure: Technical success rate of initial EUS-PCD (Endoscopic ultrasonography-guided pseudocyst drainage)
timeFrame: One day
measure: Incidence of biliary and gastrointestinal stricture
timeFrame: Five years
measure: Number and time of interventions
timeFrame: Six months
measure: Indwelling time of endoscopic and percutaneous drainage
timeFrame: Six months
measure: Success rate and operation time of surgical procedures
timeFrame: Six months
measure: Hospital stay and ICU stay
timeFrame: Six months
measure: Duration of antibiotics administration
timeFrame: Six months
measure: Cost of interventions and hospital stay
timeFrame: Six months
measure: Recurrence of WON
timeFrame: Five years
measure: Time to recurrence of WON
timeFrame: Five years
measure: Treatment duration of recurrent WON
timeFrame: Five years
measure: New onset of pseudocyst
timeFrame: Five years
measure: Treatment duration of new onset pseudocyst
timeFrame: Five years
measure: Incidence of new onset diabetes, clinical symptoms of pancreatic exocrine insufficiency, and pancreatic cancer
timeFrame: Five years
measure: The presence and timing of medications for pancreatic exocrine insufficiency
timeFrame: Five years
measure: The presence and timing of sarcopenia
timeFrame: Five years
measure: Morphological change of pancreas
timeFrame: Five years
Other outcomes:
Locations:
city: Bunkyō-Ku
country: Japan
facility: Department of Gastroenterology, The University of Tokyo Hospital
state: Tokyo
city: Bunkyō-Ku
country: Japan
facility: Department of Gastroenterology, Graduate School of Medicine, Juntendo University
state: Tokyo
city: Aichi
country: Japan
facility: Department of Gastroenterology, Aichi Medical University
city: Chiba
country: Japan
facility: Department of Gastroenterology, Graduate School of Medicine, Chiba 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 Gastroenterology and Hepatobiliary and Pancreatic Diseases, Department of Internal Medicine, 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: 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: Okinawa
country: Japan
facility: Department of Gastroenterology, Yuuai Medical Center
city: Osaka
country: Japan
facility: 2nd Department of Internal Medicine, Osaka Medical College
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: Ōsaka-sayama
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.