Immediate Necrosectomy vs. Step-up Approach for Walled-off Necrosis

Pancreatic Pseudocyst Clinical Trial

— WONDER-01  

Official title:

Immediate Necrosectomy vs. Step-up Approach After EUS-guided Drainage of Walled-off Necrosis: a Multicenter Randomized Controlled Trial (WONDER-01)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05451901
• Other study ID #: 2021005P
• Secondary ID: jRCT1032220055
• Status: Recruiting
• Phase: N/A
• Start date: July 29, 2022
• Est. completion date: April 11, 2031

Study information

• Verified date: October 2022
• 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

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: April 11, 2031
• Est. primary completion date: April 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Necrosis
• Pancreatic Pseudocyst
• Pancreatitis
• Pancreatitis, Acute Necrotizing
• Walled-off Necrosis

Intervention

Procedure:
• Immediate necrosectomy
Endoscopic ultrasonography (EUS)-guided drainage will be conducted within 72 hours from randomization. A convex-type echoendoscope is advanced to the stomach or duodenum, and the walled-off necrosis (WON) is visualized and punctured under EUS guidance. A lumen-apposing metal stent (LAMS), such as Hot AXIOS system (Boston Scientific Japan, Tokyo, Japan), is recommended for the initial EUS-guided drainage. For the immediate necrosectomy group, endoscopic necrosectomy (EN) will be performed in the same session of EUS-guided drainage using a gastroscope. The endoscope is inserted into the WON cavity through the LAMS, and necrotic tissue is removed using biopsy forceps, snare, or basket catheter. The EN procedures will be repeated until clinical improvement.
• Step-up approach
Endoscopic ultrasonography (EUS)-guided drainage will be conducted within 72 hours from randomization. A convex-type echoendoscope is advanced to the stomach or duodenum, and the walled-off necrosis (WON) is visualized and punctured under EUS guidance. A lumen-apposing metal stent (LAMS), such as Hot AXIOS system (Boston Scientific Japan, Tokyo, Japan), is recommended for the initial EUS-guided drainage. For the step-up approach group, an additional interventional procedure will be withheld for 72-96 hours after initial EUS-guided drainage. In cases without clinical improvement after 72-96 hours, additional drainage will be permitted, which includes increasing the number of stents, additional EUS-guided drainage, and performing percutaneous drainage (step-up treatment). Insufficient improvement even after two times of step-up treatment allows subsequent endoscopic necrosectomy (EN).

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 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 Gastroenterology and Hepatobiliary and Pancreatic Diseases, Department of Internal Medicine, 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 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, Yuuai Medical Center	Okinawa
Japan	2nd Department of Internal Medicine, Osaka Medical College	Osaka
Japan	Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine	Osaka-sayama
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

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	Time to clinical success from randomization	Clinical success is defined as 1) a decrease in the WON size to 3 cm or less and 2) an improvement of more than two out of the three following inflammatory markers; body temperature, white blood cell count, and C-reactive protein.	Six months
Secondary	Adverse events	All procedure-related adverse events including bleeding, perforation, peritonitis, etc.	Five years
Secondary	Mortality	Mortality from any cause	Five years
Secondary	Technical success rate of initial EUS-PCD (Endoscopic ultrasonography-guided pseudocyst drainage)	Successful placement of EUS-guided drainage including a lumen-apposing metal stent and plastic stents	One day
Secondary	Incidence of biliary and gastrointestinal stricture	Inflammatory-induced obstruction of bile duct and gastrointestinal tract	Five years
Secondary	Number and time of interventions	Total number of interventions and total procedure time	Six months
Secondary	Indwelling time of endoscopic and percutaneous drainage	Indwelling period of stents and drainage tube	Six months
Secondary	Success rate and operation time of surgical procedures	Success rate of surgeries associated with WON and total operation time	Six months
Secondary	Hospital stay and ICU stay	Total hospitalization days and total ICU stay	Six months
Secondary	Duration of antibiotics administration	Total administration days of antibiotics	Six months
Secondary	Cost of interventions and hospital stay	Total cost of interventions and total cost of hospitalization	Six months
Secondary	Recurrence of WON	Incidence of recurrence of WON	Five years
Secondary	Time to recurrence of WON	Time from clinical success to recurrence of WON	Five years
Secondary	Treatment duration of recurrent WON	Total treatment period for recurrent WON	Five years
Secondary	New onset of pseudocyst	Incidence of new-onset pancreatic pseudocyst	Five years
Secondary	Treatment duration of new onset pseudocyst	Total treatment period for new-onset pancreatic pseudocyst	Five years
Secondary	Incidence of new onset diabetes, clinical symptoms of pancreatic exocrine insufficiency, and pancreatic cancer	New-onset diabetes mellitus, pancreatic cancer, and clinical symptoms associated with pancreatic exocrine insufficiency, such as steatorrhea , constipation, diarrhea, maldigestion, flatulence, and tenesmus	Five years
Secondary	The presence and timing of medications for pancreatic exocrine insufficiency	The start of medications for pancreatic exocrine insufficiency and the date	Five years
Secondary	The presence and timing of sarcopenia	The presence of sarcopenia and the date of diagnosis	Five years
Secondary	Morphological change of pancreas	Change in the morphology and the volume of pancreas	Five years