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Immediate Necrosectomy vs. Step-up Approach for Walled-off Necrosis (WONDER-01)

Primary Purpose

Pancreatic Fluid Collection, Walled-off Necrosis, Pancreatitis, Acute Necrotizing

Status
Recruiting
Phase
Not Applicable
Locations
Japan
Study Type
Interventional
Intervention
Immediate necrosectomy
Step-up approach
Sponsored by
Tokyo University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Fluid Collection focused on measuring Endosonography, Drainage, Stents, Endoscopic necrosectomy, Step-up approach

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Department of Gastroenterology, The University of Tokyo Hospital
  • Department of Gastroenterology, Graduate School of Medicine, Juntendo UniversityRecruiting
  • Department of Gastroenterology, Aichi Medical UniversityRecruiting
  • Department of Gastroenterology, Graduate School of Medicine, Chiba UniversityRecruiting
  • Department of Gastroenterology, Gifu Municipal HospitalRecruiting
  • Department of Gastroenterology, Gifu Prefectural General Medical CenterRecruiting
  • First Department of Internal Medicine, Gifu University Hospital
  • Division of Gastroenterology and Hepatobiliary and Pancreatic Diseases, Department of Internal Medicine, Hyogo Medical UniversityRecruiting
  • Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa UniversityRecruiting
  • Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental SciencesRecruiting
  • Department of Gastroenterology, Kameda Medical CenterRecruiting
  • Department of Gastroenterological Endoscopy, Kanazawa Medical University
  • Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University
  • Department of Gastroenterology, Teikyo University Mizonokuchi Hospital
  • Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of MedicineRecruiting
  • Department of Gastroenterology, Yuuai Medical CenterRecruiting
  • 2nd Department of Internal Medicine, Osaka Medical College
  • Department of Gastroenterology and Hepatology, Hokkaido University HospitalRecruiting
  • Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine
  • Third Department of Internal Medicine, University of ToyamaRecruiting
  • Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Immediate necrosectomy

Step-up approach

Arm Description

Endoscopic necrosectomy will be conducted in the same session of EUS-guided drainage (or at least within 72 hours of randomization) and be repeated until clinical success.

Step-up treatment will be conducted if a patient's condition does not improve after EUS-guided drainage. The step-up approach includes increasing the number of stents, adding another EUS-guided drainage, and performing percutaneous drainage after 72-96 hours of the initial drainage. Endoscopic necrosectomy is considered when clinical improvement is not observed even after two times of step-up treatment.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Adverse events
All procedure-related adverse events including bleeding, perforation, peritonitis, etc.
Mortality
Mortality from any cause
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
Incidence of biliary and gastrointestinal stricture
Inflammatory-induced obstruction of bile duct and gastrointestinal tract
Number and time of interventions
Total number of interventions and total procedure time
Indwelling time of endoscopic and percutaneous drainage
Indwelling period of stents and drainage tube
Success rate and operation time of surgical procedures
Success rate of surgeries associated with WON and total operation time
Hospital stay and ICU stay
Total hospitalization days and total ICU stay
Duration of antibiotics administration
Total administration days of antibiotics
Cost of interventions and hospital stay
Total cost of interventions and total cost of hospitalization
Recurrence of WON
Incidence of recurrence of WON
Time to recurrence of WON
Time from clinical success to recurrence of WON
Treatment duration of recurrent WON
Total treatment period for recurrent WON
New onset of pseudocyst
Incidence of new-onset pancreatic pseudocyst
Treatment duration of new onset pseudocyst
Total treatment period for new-onset pancreatic pseudocyst
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
The presence and timing of medications for pancreatic exocrine insufficiency
The start of medications for pancreatic exocrine insufficiency and the date
The presence and timing of sarcopenia
The presence of sarcopenia and the date of diagnosis
Morphological change of pancreas
Change in the morphology and the volume of pancreas

Full Information

First Posted
July 3, 2022
Last Updated
October 26, 2022
Sponsor
Tokyo University
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1. Study Identification

Unique Protocol Identification Number
NCT05451901
Brief Title
Immediate Necrosectomy vs. Step-up Approach for Walled-off Necrosis
Acronym
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 29, 2022 (Actual)
Primary Completion Date
April 1, 2025 (Anticipated)
Study Completion Date
April 11, 2031 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tokyo University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Fluid Collection, Walled-off Necrosis, Pancreatitis, Acute Necrotizing, Pancreatic Pseudocyst
Keywords
Endosonography, Drainage, Stents, Endoscopic necrosectomy, Step-up approach

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Immediate necrosectomy
Arm Type
Experimental
Arm Description
Endoscopic necrosectomy will be conducted in the same session of EUS-guided drainage (or at least within 72 hours of randomization) and be repeated until clinical success.
Arm Title
Step-up approach
Arm Type
Active Comparator
Arm Description
Step-up treatment will be conducted if a patient's condition does not improve after EUS-guided drainage. The step-up approach includes increasing the number of stents, adding another EUS-guided drainage, and performing percutaneous drainage after 72-96 hours of the initial drainage. Endoscopic necrosectomy is considered when clinical improvement is not observed even after two times of step-up treatment.
Intervention Type
Procedure
Intervention Name(s)
Immediate necrosectomy
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Step-up approach
Intervention Description
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).
Primary Outcome Measure Information:
Title
Time to clinical success from randomization
Description
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.
Time Frame
Six months
Secondary Outcome Measure Information:
Title
Adverse events
Description
All procedure-related adverse events including bleeding, perforation, peritonitis, etc.
Time Frame
Five years
Title
Mortality
Description
Mortality from any cause
Time Frame
Five years
Title
Technical success rate of initial EUS-PCD (Endoscopic ultrasonography-guided pseudocyst drainage)
Description
Successful placement of EUS-guided drainage including a lumen-apposing metal stent and plastic stents
Time Frame
One day
Title
Incidence of biliary and gastrointestinal stricture
Description
Inflammatory-induced obstruction of bile duct and gastrointestinal tract
Time Frame
Five years
Title
Number and time of interventions
Description
Total number of interventions and total procedure time
Time Frame
Six months
Title
Indwelling time of endoscopic and percutaneous drainage
Description
Indwelling period of stents and drainage tube
Time Frame
Six months
Title
Success rate and operation time of surgical procedures
Description
Success rate of surgeries associated with WON and total operation time
Time Frame
Six months
Title
Hospital stay and ICU stay
Description
Total hospitalization days and total ICU stay
Time Frame
Six months
Title
Duration of antibiotics administration
Description
Total administration days of antibiotics
Time Frame
Six months
Title
Cost of interventions and hospital stay
Description
Total cost of interventions and total cost of hospitalization
Time Frame
Six months
Title
Recurrence of WON
Description
Incidence of recurrence of WON
Time Frame
Five years
Title
Time to recurrence of WON
Description
Time from clinical success to recurrence of WON
Time Frame
Five years
Title
Treatment duration of recurrent WON
Description
Total treatment period for recurrent WON
Time Frame
Five years
Title
New onset of pseudocyst
Description
Incidence of new-onset pancreatic pseudocyst
Time Frame
Five years
Title
Treatment duration of new onset pseudocyst
Description
Total treatment period for new-onset pancreatic pseudocyst
Time Frame
Five years
Title
Incidence of new onset diabetes, clinical symptoms of pancreatic exocrine insufficiency, and pancreatic cancer
Description
New-onset diabetes mellitus, pancreatic cancer, and clinical symptoms associated with pancreatic exocrine insufficiency, such as steatorrhea , constipation, diarrhea, maldigestion, flatulence, and tenesmus
Time Frame
Five years
Title
The presence and timing of medications for pancreatic exocrine insufficiency
Description
The start of medications for pancreatic exocrine insufficiency and the date
Time Frame
Five years
Title
The presence and timing of sarcopenia
Description
The presence of sarcopenia and the date of diagnosis
Time Frame
Five years
Title
Morphological change of pancreas
Description
Change in the morphology and the volume of pancreas
Time Frame
Five years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yousuke Nakai
Phone
+81-3-3815-5411
Email
ynakai-tky@umin.ac.jp
First Name & Middle Initial & Last Name or Official Title & Degree
Tomotaka Saito
Phone
+81-3-3815-5411
Email
tomsaito-gi@umin.ac.jp
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yousuke Nakai
Organizational Affiliation
Department of Endoscopy and Endoscopic Surgery, Graduate School of Medicine, The University of Tokyo
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Gastroenterology, The University of Tokyo Hospital
City
Bunkyō-Ku
State/Province
Tokyo
ZIP/Postal Code
113-8655
Country
Japan
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yousuke Nakai
First Name & Middle Initial & Last Name & Degree
Tomotaka Saito
Phone
+81-3-3815-5411
Email
tomsaito-gi@umin.ac.jp
Facility Name
Department of Gastroenterology, Graduate School of Medicine, Juntendo University
City
Bunkyō-Ku
State/Province
Tokyo
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hiroyuki Isayama
First Name & Middle Initial & Last Name & Degree
Toshio Fujisawa
First Name & Middle Initial & Last Name & Degree
Sho Takahashi
Facility Name
Department of Gastroenterology, Aichi Medical University
City
Aichi
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tadahisa Inoue
Facility Name
Department of Gastroenterology, Graduate School of Medicine, Chiba University
City
Chiba
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hiroshi Ohyama
First Name & Middle Initial & Last Name & Degree
Koji Takahashi
Facility Name
Department of Gastroenterology, Gifu Municipal Hospital
City
Gifu
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Keisuke Iwata
First Name & Middle Initial & Last Name & Degree
Mitsuru Okuno
Facility Name
Department of Gastroenterology, Gifu Prefectural General Medical Center
City
Gifu
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Akinori Maruta
First Name & Middle Initial & Last Name & Degree
Kensaku Yoshida
Facility Name
First Department of Internal Medicine, Gifu University Hospital
City
Gifu
Country
Japan
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Takuji Iwashita
First Name & Middle Initial & Last Name & Degree
Shinya Uemura
Facility Name
Division of Gastroenterology and Hepatobiliary and Pancreatic Diseases, Department of Internal Medicine, Hyogo Medical University
City
Hyōgo
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hideyuki Shiomi
First Name & Middle Initial & Last Name & Degree
Shogo Ota
First Name & Middle Initial & Last Name & Degree
Ryota Nakano
Facility Name
Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University
City
Kagawa
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hideki Kamada
First Name & Middle Initial & Last Name & Degree
Daisuke Namima
Facility Name
Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences
City
Kagoshima
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shinichi Hashimoto
First Name & Middle Initial & Last Name & Degree
Makoto Hinokuchi
Facility Name
Department of Gastroenterology, Kameda Medical Center
City
Kamogawa
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Toshiyasu Shiratori
First Name & Middle Initial & Last Name & Degree
So Nakaji
Facility Name
Department of Gastroenterological Endoscopy, Kanazawa Medical University
City
Kanazawa
Country
Japan
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tsuyoshi Mukai
Facility Name
Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University
City
Kawagoe
Country
Japan
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Saburo Matsubara
First Name & Middle Initial & Last Name & Degree
Keito Nakagawa
Facility Name
Department of Gastroenterology, Teikyo University Mizonokuchi Hospital
City
Kawasaki
Country
Japan
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shinpei Doi
First Name & Middle Initial & Last Name & Degree
Nobuhiro Katsukura
Facility Name
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine
City
Kobe
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Atsuhiro Masuda
First Name & Middle Initial & Last Name & Degree
Masahiro Tsujimae
Facility Name
Department of Gastroenterology, Yuuai Medical Center
City
Okinawa
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kenji Chinen
Facility Name
2nd Department of Internal Medicine, Osaka Medical College
City
Osaka
Country
Japan
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Takeshi Ogura
First Name & Middle Initial & Last Name & Degree
Atsushi Okuda
Facility Name
Department of Gastroenterology and Hepatology, Hokkaido University Hospital
City
Sapporo
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Masaki Kuwatani
Facility Name
Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine
City
Tokyo
Country
Japan
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hirofumi Kogure
First Name & Middle Initial & Last Name & Degree
Kei Saito
Facility Name
Third Department of Internal Medicine, University of Toyama
City
Toyama
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ichiro Yasuda
First Name & Middle Initial & Last Name & Degree
Nobuhiko Hayashi
Facility Name
Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine
City
Ōsaka-sayama
Country
Japan
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mamoru Takenaka
First Name & Middle Initial & Last Name & Degree
Shunsuke Omoto

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
23100216
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.
Results Reference
background

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

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