NCT05451901

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
70

participants targeted

Target at P50-P75 for not_applicable

Timeline
60mo left

Started Jul 2022

Longer than P75 for not_applicable

Geographic Reach
1 country

21 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress43%
Jul 2022Apr 2031

First Submitted

Initial submission to the registry

July 3, 2022

Completed
8 days until next milestone

First Posted

Study publicly available on registry

July 11, 2022

Completed
18 days until next milestone

Study Start

First participant enrolled

July 29, 2022

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2025

Completed
6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 11, 2031

Expected
Last Updated

October 27, 2022

Status Verified

October 1, 2022

Enrollment Period

2.7 years

First QC Date

July 3, 2022

Last Update Submit

October 26, 2022

Conditions

Keywords

EndosonographyDrainageStentsEndoscopic necrosectomyStep-up approach

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (19)

  • Adverse events

    Five years

  • Mortality

    Five years

  • Technical success rate of initial EUS-PCD (Endoscopic ultrasonography-guided pseudocyst drainage)

    One day

  • Incidence of biliary and gastrointestinal stricture

    Five years

  • Number and time of interventions

    Six months

  • +14 more secondary outcomes

Study Arms (2)

Immediate necrosectomy

EXPERIMENTAL

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.

Procedure: Immediate necrosectomy

Step-up approach

ACTIVE COMPARATOR

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.

Procedure: Step-up approach

Interventions

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.

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 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).

Step-up approach

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (21)

Department of Gastroenterology, The University of Tokyo Hospital

Bunkyō-Ku, Tokyo, 113-8655, Japan

NOT YET RECRUITING

Department of Gastroenterology, Graduate School of Medicine, Juntendo University

Bunkyō-Ku, Tokyo, Japan

RECRUITING

Department of Gastroenterology, Aichi Medical University

Aichi, Japan

RECRUITING

Department of Gastroenterology, Graduate School of Medicine, Chiba University

Chiba, Japan

RECRUITING

Department of Gastroenterology, Gifu Municipal Hospital

Gifu, Japan

RECRUITING

Department of Gastroenterology, Gifu Prefectural General Medical Center

Gifu, Japan

RECRUITING

First Department of Internal Medicine, Gifu University Hospital

Gifu, Japan

NOT YET RECRUITING

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

Hyōgo, Japan

RECRUITING

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

Kagawa, Japan

RECRUITING

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

Kagoshima, Japan

RECRUITING

Department of Gastroenterology, Kameda Medical Center

Kamogawa, Japan

RECRUITING

Department of Gastroenterological Endoscopy, Kanazawa Medical University

Kanazawa, Japan

NOT YET RECRUITING

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

Kawagoe, Japan

NOT YET RECRUITING

Department of Gastroenterology, Teikyo University Mizonokuchi Hospital

Kawasaki, Japan

NOT YET RECRUITING

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

Kobe, Japan

RECRUITING

Department of Gastroenterology, Yuuai Medical Center

Okinawa, Japan

RECRUITING

2nd Department of Internal Medicine, Osaka Medical College

Osaka, Japan

NOT YET RECRUITING

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine

Ōsaka-sayama, Japan

NOT YET RECRUITING

Department of Gastroenterology and Hepatology, Hokkaido University Hospital

Sapporo, Japan

RECRUITING

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

Tokyo, Japan

NOT YET RECRUITING

Third Department of Internal Medicine, University of Toyama

Toyama, Japan

RECRUITING

Related Publications (2)

  • 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.

    PMID: 23100216BACKGROUND
  • 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.

MeSH Terms

Conditions

Pancreatitis, Acute NecrotizingPancreatic Pseudocyst

Condition Hierarchy (Ancestors)

PancreatitisPancreatic DiseasesDigestive System DiseasesPancreatic CystCystsNeoplasms

Study Officials

  • Yousuke Nakai

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

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate professor, Department of Endoscopy and Endoscopic Surgery, The University of Tokyo Hospital

Study Record Dates

First Submitted

July 3, 2022

First Posted

July 11, 2022

Study Start

July 29, 2022

Primary Completion

April 1, 2025

Study Completion (Estimated)

April 11, 2031

Last Updated

October 27, 2022

Record last verified: 2022-10

Data Sharing

IPD Sharing
Will not share

Locations