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

NCT ID: NCT05451901

Last Updated: 2022-10-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-29
• Study Completion Date: 2031-04-11

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Immediate necrosectomy

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.

Group Type: EXPERIMENTAL

Immediate necrosectomy

Intervention Type: PROCEDURE

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

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.

Group Type: ACTIVE_COMPARATOR

Step-up approach

Intervention Type: PROCEDURE

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).

Interventions

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.

Intervention Type: PROCEDURE

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).

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tokyo University

OTHER

Sponsor Role: lead

Responsible Party

Yousuke Nakai

Associate professor, Department of Endoscopy and Endoscopic Surgery, The University of Tokyo Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yousuke Nakai

Role: PRINCIPAL_INVESTIGATOR

Department of Endoscopy and Endoscopic Surgery, Graduate School of Medicine, The University of Tokyo

Locations

Department of Gastroenterology, The University of Tokyo Hospital

Bunkyō-Ku, Tokyo, Japan

Site Status: NOT_YET_RECRUITING

Department of Gastroenterology, Graduate School of Medicine, Juntendo University

Bunkyō-Ku, Tokyo, Japan

Site Status: RECRUITING

Department of Gastroenterology, Aichi Medical University

Aichi, , Japan

Site Status: RECRUITING

Department of Gastroenterology, Graduate School of Medicine, Chiba University

Chiba, , Japan

Site Status: RECRUITING

Department of Gastroenterology, Gifu Municipal Hospital

Gifu, , Japan

Site Status: RECRUITING

Department of Gastroenterology, Gifu Prefectural General Medical Center

Gifu, , Japan

Site Status: RECRUITING

First Department of Internal Medicine, Gifu University Hospital

Gifu, , Japan

Site Status: NOT_YET_RECRUITING

Division of Gastroenterology and Hepatobiliary and Pancreatic Diseases, Department of Internal Medicine, Hyogo Medical University

Hyōgo, , Japan

Site Status: RECRUITING

Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University

Kagawa, , Japan

Site Status: RECRUITING

Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences

Kagoshima, , Japan

Site Status: RECRUITING

Department of Gastroenterology, Kameda Medical Center

Kamogawa, , Japan

Site Status: RECRUITING

Department of Gastroenterological Endoscopy, Kanazawa Medical University

Kanazawa, , Japan

Site Status: NOT_YET_RECRUITING

Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University

Kawagoe, , Japan

Site Status: NOT_YET_RECRUITING

Department of Gastroenterology, Teikyo University Mizonokuchi Hospital

Kawasaki, , Japan

Site Status: NOT_YET_RECRUITING

Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine

Kobe, , Japan

Site Status: RECRUITING

Department of Gastroenterology, Yuuai Medical Center

Okinawa, , Japan

Site Status: RECRUITING

2nd Department of Internal Medicine, Osaka Medical College

Osaka, , Japan

Site Status: NOT_YET_RECRUITING

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine

Ōsaka-sayama, , Japan

Site Status: NOT_YET_RECRUITING

Department of Gastroenterology and Hepatology, Hokkaido University Hospital

Sapporo, , Japan

Site Status: RECRUITING

Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine

Tokyo, , Japan

Site Status: NOT_YET_RECRUITING

Third Department of Internal Medicine, University of Toyama

Toyama, , Japan

Site Status: RECRUITING

Countries

Japan

Central Contacts

Yousuke Nakai

Role: CONTACT

ynakai-tky@umin.ac.jp

+81-3-3815-5411

Tomotaka Saito

Role: CONTACT

tomsaito-gi@umin.ac.jp

+81-3-3815-5411

Facility Contacts

Yousuke Nakai

Role: primary

Tomotaka Saito

Role: backup

tomsaito-gi@umin.ac.jp

+81-3-3815-5411

Hiroyuki Isayama

Role: primary

Toshio Fujisawa

Role: backup

Tadahisa Inoue

Role: primary

Hiroshi Ohyama

Role: primary

Koji Takahashi

Role: backup

Keisuke Iwata

Role: primary

Mitsuru Okuno

Role: backup

Akinori Maruta

Role: primary

Kensaku Yoshida

Role: backup

Takuji Iwashita

Role: primary

Shinya Uemura

Role: backup

Hideyuki Shiomi

Role: primary

Shogo Ota

Role: backup

Hideki Kamada

Role: primary

Daisuke Namima

Role: backup

Shinichi Hashimoto

Role: primary

Makoto Hinokuchi

Role: backup

Toshiyasu Shiratori

Role: primary

So Nakaji

Role: backup

Tsuyoshi Mukai

Role: primary

Saburo Matsubara

Role: primary

Keito Nakagawa

Role: backup

Shinpei Doi

Role: primary

Nobuhiro Katsukura

Role: backup

Atsuhiro Masuda

Role: primary

Masahiro Tsujimae

Role: backup

Kenji Chinen

Role: primary

Takeshi Ogura

Role: primary

Atsushi Okuda

Role: backup

Mamoru Takenaka

Role: primary

Shunsuke Omoto

Role: backup

Masaki Kuwatani

Role: primary

Hirofumi Kogure

Role: primary

Kei Saito

Role: backup

Ichiro Yasuda

Role: primary

Nobuhiko Hayashi

Role: backup

References

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.

Reference Type: BACKGROUND

PMID: 23100216 (View on PubMed)

Sato T, Saito T, Takenaka M, Iwashita T, Shiomi H, Fujisawa T, Hayashi N, Iwata K, Maruta A, Mukai T, Masuda A, Matsubara S, Hamada T, Inoue T, Ohyama H, Kuwatani M, Kamada H, Hashimoto S, Shiratori T, Yamada R, Kogure H, Ogura T, Nakahara K, Doi S, Chinen K, Isayama H, Yasuda I, Nakai Y; WONDERFUL study group in Japan, collaborators. WONDER-01: immediate necrosectomy vs. drainage-oriented step-up approach after endoscopic ultrasound-guided drainage of walled-off necrosis-study protocol for a multicentre randomised controlled trial. Trials. 2023 May 24;24(1):352. doi: 10.1186/s13063-023-07377-y.

Reference Type: DERIVED

PMID: 37226252 (View on PubMed)

Other Identifiers

jRCT1032220055

Identifier Type: REGISTRY

Identifier Source: secondary_id

2021005P

Identifier Type: -

Identifier Source: org_study_id