Encapsulation-oriented vs. Timing-oriented Strategies for Necrotizing Pancreatitis

NCT07106346 | Not Yet Recruiting DMC

• 1 other identifier: 2025002P
• Study Type: interventional
• Target: 224
• Locations: 1 country
• Sites: 36

Brief Summary

This multicenter, randomized controlled trial (WONDER-03 study) investigates the optimal timing for endoscopic ultrasound (EUS)-guided drainage in patients with necrotizing pancreatitis. Although current guidelines recommend delaying drainage until at least four weeks after the onset of acute pancreatitis to allow for encapsulation of necrosis, recent observational data suggest that the degree of encapsulation itself may more strongly influence treatment success and safety. In this trial, patients are randomly assigned to one of two groups: an encapsulation-oriented group, in which EUS-guided drainage is performed when imaging confirms ≥80% encapsulation of the necrotic collection with symptoms, and a timing-oriented group, in which drainage is performed at four to five weeks after disease onset, regardless of encapsulation status. The primary endpoint is clinical success within 180 days, defined as both radiologic resolution of necrosis and improvement in symptoms. Secondary endpoints include adverse event rates, recurrence of fluid collections, technical and clinical success rates, and healthcare resource use. This study aims to determine whether a strategy based on encapsulation leads to better clinical outcomes than the conventional time-based approach and may help establish a new evidence-based treatment algorithm for necrotizing pancreatitis.

Conditions

Walled Off Necrosis; Pancreatitis; Acute Necrotic Collection; Necrotizing Pancreatitis; Pancreatitis, Acute Necrotizing

Keywords

Endosonography; Drainage; Walled Off Necrosis; necrotizing pancreatitis; pancreatitis

Outcome Measures

Primary Outcomes (1)

• Clinical success rate within 180 days after randomization

  Defined as reduction of necrotic collection to ≤2 cm on imaging and resolution of symptoms that required intervention (infection: at least two out of the following inflammatory indicators: body temperature, white blood cell count, and C-reactive protein, pain, GI obstruction, or jaundice).

  Six months

Secondary Outcomes (22)

• Rate of procedure-related adverse events

  5 years

• All-cause mortality

  5 years

• Time to clinical success

  180 days

• Technical success of initial EUS-guided drainage

  At the time of first EUS-guided drainage procedure

• Incidence of biliary or gastrointestinal stricture

  5 years

Study Arms (2)

Encapsulation-Oriented Group

EXPERIMENTAL

The timing of endoscopic intervention for necrotizing pancreatitis is determined based on the degree of encapsulation

Procedure: The timing of endoscopic intervention for necrotizing pancreatitis is determined based on the degree of encapsulation

Timing-Oriented Group

ACTIVE COMPARATOR

EUS-guided drainage based on the interval from the onset of acute pancreatitis

Procedure: EUS-guided drainage based on the interval from the onset of acute pancreatitis

Interventions

The timing of endoscopic intervention for necrotizing pancreatitis is determined based on the degree of encapsulation PROCEDURE

In the encapsulation-oriented group, participants undergo EUS-guided drainage of necrotizing pancreatitis when the degree of encapsulation reaches ≥80%, as confirmed by cross-sectional imaging (preferably contrast-enhanced CT). Imaging is repeated every 7-10 days after enrollment to assess encapsulation. Once sufficient encapsulation is observed and the patient presents with symptoms such as infection, abdominal pain, GOO or biliary obstruction, endoscopic drainage is performed. Drainage is typically performed using a lumen-apposing metal stent (LAMS) placed under EUS guidance, often accompanied by placement of an external drain. Step-up therapy, including endoscopic necrosectomy or additional drainage procedures, may be used if symptoms do not improve. If the patient improves with conservative therapy before encapsulation is achieved, drainage may be deferred. Endoscopic/percutaneous interventions should, in principle, be discussed with the expert panel beforehand.

Encapsulation-Oriented Group

EUS-guided drainage based on the interval from the onset of acute pancreatitis PROCEDURE

In the timing-oriented group, participants undergo EUS-guided drainage of necrotizing pancreatitis at 4 to 5 weeks after the onset of acute pancreatitis, regardless of the degree of encapsulation. Drainage is performed only in symptomatic patients who meet predefined clinical criteria, such as signs of infection, significant pain, GOO, or biliary obstruction. Imaging is performed before the procedure. The standard approach involves placing a LAMS under EUS guidance, optionally supplemented by external drains. If symptoms do not improve, step-up interventions such as endoscopic necrosectomy, percutaneous drainage may be considered. If inflammation and symptoms improve with conservative treatment (e.g., antibiotics), EUS-guided drainage may be omitted. Conversely, even before 4-5 weeks from onset, early drainage is allowed if conservative treatment is deemed insufficient by the attending physician. In principle, intervention decisions should be discussed with the expert panel.

Timing-Oriented Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with necrotizing pancreatitis according to the revised Atlanta classification, confirmed by contrast-enhanced CT (plain CT or MRI may be substituted if contrast-enhanced CT is not feasible).
• Within 28 days of onset of acute pancreatitis.
• Age ≥ 18 years at the time of consent, regardless of sex.
• Provided written informed consent from the patient or a legally authorized representative after sufficient explanation.
• Patients who are either hospitalized or being followed as outpatients at participating study institutions.

You may not qualify if:

• Unknown date of onset of acute pancreatitis.
• Patients who have already undergone transluminal drainage with stent placement for necrotizing pancreatitis.
• Diagnosis of chronic pancreatitis.
• Patients for whom endoscopic treatment is deemed unsafe.
• Pregnant women.
• Patients deemed inappropriate for the study by the principal investigator or sub-investigator.

Sponsors & Collaborators

• Tokyo University: lead
• Tokyo Women's Medical University: collaborator

Study Sites (36)

Department of Gastroenterology, Aichi Medical University

Aichi, Japan, Japan

Location

Department of Gastroenterology, Graduate School of Medicine, Chiba University

Chiba, Japan, Japan

Location

Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University

Fukuoka, Japan, Japan

Location

Department of Gastroenterology, Gifu Municipal Hospital

Gifu, Japan, Japan

Location

Department of Gastroenterology, Gifu Prefectural General Medical Center

Gifu, Japan, Japan

Location

First Department of Internal Medicine, Gifu University Hospital

Gifu, Japan, Japan

Location

Department of Gastroenterology and Hepatology, Hokkaido University Hospital

Hokkaido, Japan, Japan

Location

Division of Hepatobiliary and Pancreatic Diseases, Department of Gastroenterology, Hyogo MedicalUniversity

Hyōgo, Japan, Japan

Location

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

Kagawa, Japan, Japan

Location

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

Kagoshima, Japan, Japan

Location

Department of Gastroenterology, Kameda Medical Center

Kamogawa, Japan, Japan

Location

Department of Gastroenterology, St. Marianna University School of Medicine

Kanagawa, Japan, Japan

Location

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

Kawagoe, Japan, Japan

Location

Department of Gastroenterology, Teikyo University Mizonokuchi Hospital

Kawasaki, Japan, Japan

Location

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

Kobe, Japan, Japan

Location

Department of Gastroenterology and Hepatology, Mie University Hospital

Mie, Japan, Japan

Location

Department of Gastroenterology and Hepatology, Okayama University Hospital

Okayama, Japan, Japan

Location

2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University

Osaka, Japan, Japan

Location

Department of Gastroenterology and Hepatology, Kansai Medical University Medical Center

Osaka, Japan, Japan

Location

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine

Osaka, Japan, Japan

Location

Department of Gastroenterology, Shiga University of Medical Science

Shiga, Japan, Japan

Location

Department of Gastroenterology, Tokyo Women's Medical University

Tokyo, Japan, Japan

Location

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

Tokyo, Japan, Japan

Location

Department of Gastroenterology, Wakayama Medical University School of Medicine

Wakayama, Japan, Japan

Location

Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences

Aichi, Tokyo, Japan

Location

Department of Gastroenterology, Nagoya University

Aichi, Tokyo, Japan

Location

Department of Gastroenterology, The University of Tokyo Hospital

Bunkyō-Ku, Tokyo, 113-8655, Japan

Location

Department of Gastroenterology, Graduate School of Medicine, Juntendo University

Bunkyō-Ku, Tokyo, Japan

Location

Department of Gastroenterology, Fukuoka University

Fukuoka, Tokyo, Japan

Location

Department of Gastroenterology, Kurume University

Fukuoka, Tokyo, Japan

Location

Department of Gastroenterology, Matsunami General Hospital

Gifu, Tokyo, Japan

Location

Department of Gastroenterology, Hiroshima University

Hiroshima, Tokyo, Japan

Location

Department of Gastroenterology, JA Onomichi General Hospital

Hiroshima, Tokyo, Japan

Location

Gastroenterology Center, Yokohama City University Medical Center

Kanagawa, Tokyo, Japan

Location

Department of Gastrointestinal, Hepatobiliary and Pancreatic Diseases, Sendai City Medical Center (Sendai Open Hospital)

Miyagi, Tokyo, Japan

Location

Third Department of Internal Medicine, University of Toyama

Toyama, Japan

Location

Related 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.

  PMID: 23100216 BACKGROUND

MeSH Terms

Conditions

Pancreatitis; Pancreatitis, Acute Necrotizing

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases

Study Officials

• Yousuke Nakai

  Department of Gastroenterology, Tokyo Women's Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yousuke Nakai

CONTACT

+81-3-3353-8111; ynakai-tky@umin.ac.jp

Tomotaka Saito

CONTACT

+81-3-3815-5411; tomsaito-gi@umin.ac.jp

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: Professor, Department of Gastroenterology, Tokyo Women's Medical University

Study Record Dates

• First Submitted: July 30, 2025
• First Posted: August 6, 2025
• Study Start: August 5, 2025
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: August 6, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

JP (36)