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

NCT ID: NCT07106346

Last Updated: 2025-08-06

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 224 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-05
• Study Completion Date: 2028-07-31

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.

Detailed Description

Necrotizing pancreatitis is a severe and potentially life-threatening condition characterized by pancreatic and/or peripancreatic tissue necrosis. Endoscopic ultrasound (EUS)-guided transmural drainage has become widely adopted as a minimally invasive approach for the management of symptomatic necrotizing pancreatitis, particularly in cases of infected collections or organ compression. Traditionally, clinical guidelines have recommended delaying such drainage procedures until four weeks after the onset of acute pancreatitis, under the assumption that encapsulation of the necrotic tissue during this time enhances safety and technical success. However, this timing-based strategy lacks robust prospective validation and may not be optimal for all patients.

Recent data from multicenter cohort studies conducted in Japan have indicated that the degree of encapsulation at the time of drainage may be a more critical factor than the elapsed time since disease onset. In these studies, patients with ≥80% encapsulation demonstrated significantly higher rates of clinical success and lower complication rates compared to those with partial or no encapsulation, regardless of the timing of intervention. This observation suggests that the current standard approach, which relies solely on time from onset, may not adequately capture individual patient readiness for intervention.

The WONDER-03 study is designed as a multicenter, open-label, randomized controlled trial to compare two treatment strategies in patients with necrotizing pancreatitis. Participants are randomly assigned to either the encapsulation-oriented group or the timing-oriented group. In the encapsulation-oriented group, EUS-guided drainage is performed once imaging, preferably contrast-enhanced CT, confirms that the necrotic collection is at least 80% encapsulated and the patient presents with symptoms such as infection, abdominal pain, gastrointestinal obstruction, or biliary obstruction. In the timing-oriented group, drainage is scheduled for four to five weeks after the onset of acute pancreatitis if the patient is symptomatic, irrespective of the encapsulation status.

Eligible patients must be 18 years or older, have a diagnosis of necrotizing pancreatitis based on imaging, and be enrolled within 28 days of disease onset. Exclusion criteria include unclear onset timing, prior drainage procedures, a diagnosis of chronic pancreatitis, contraindications to endoscopic treatment, or pregnancy. Randomization is stratified by participating institution and the presence of organ failure.

The primary outcome of the study is clinical success within 180 days of randomization, defined as both a reduction in the maximum diameter of the necrotic collection to ≤2 cm on CT or MRI, and resolution of the symptoms that necessitated intervention. These may include normalization of inflammatory markers in infected cases, relief of abdominal pain or gastrointestinal obstruction, or resolution of biliary obstruction.

Secondary outcomes include the incidence of procedure-related complications, technical success of EUS drainage, time to clinical success, recurrence of pancreatic fluid collections, mortality, total number and duration of interventions, need for surgery, length of hospitalization and ICU stay, duration of antibiotic therapy, and related medical costs. In addition, long-term outcomes such as the development of diabetes, exocrine pancreatic insufficiency, sarcopenia, and pancreatic cancer will be monitored over a follow-up period of five years.

The trial also incorporates centralized oversight through an expert panel, which assists in evaluating imaging findings to confirm eligibility and encapsulation status. All procedures are performed by experienced endoscopists, and treatment protocols, including use of lumen-apposing metal stents (LAMS), necrosectomy, and step-up interventions, are standardized across sites.

By directly comparing the two strategies in a prospective, randomized setting, this study aims to generate high-quality evidence to guide clinical decision-making in the management of necrotizing pancreatitis. If encapsulation-oriented timing proves superior, it could shift clinical practice toward a more individualized, pathology-driven approach, improving patient outcomes while reducing the risk of complications and unnecessary delays in treatment.

Conditions

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

Study Design

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

Study Groups

Encapsulation-Oriented Group

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

Group Type: EXPERIMENTAL

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

Intervention Type: 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.

Timing-Oriented Group

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

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: 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.

Interventions

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

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.

Intervention Type: PROCEDURE

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

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.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

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

Sponsors

Tokyo Women's Medical University

OTHER

Sponsor Role: collaborator

Tokyo University

OTHER

Sponsor Role: lead

Responsible Party

Yousuke Nakai

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

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yousuke Nakai

Role: PRINCIPAL_INVESTIGATOR

Department of Gastroenterology, Tokyo Women's Medical University

Locations

Department of Gastroenterology, Aichi Medical University

Aichi, Japan, Japan

Department of Gastroenterology, Graduate School of Medicine, Chiba University

Chiba, Japan, Japan

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

Fukuoka, Japan, Japan

Department of Gastroenterology, Gifu Municipal Hospital

Gifu, Japan, Japan

Department of Gastroenterology, Gifu Prefectural General Medical Center

Gifu, Japan, Japan

First Department of Internal Medicine, Gifu University Hospital

Gifu, Japan, Japan

Department of Gastroenterology and Hepatology, Hokkaido University Hospital

Hokkaido, Japan, Japan

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

Hyōgo, Japan, Japan

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

Kagawa, Japan, Japan

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

Kagoshima, Japan, Japan

Department of Gastroenterology, Kameda Medical Center

Kamogawa, Japan, Japan

Department of Gastroenterology, St. Marianna University School of Medicine

Kanagawa, Japan, Japan

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

Kawagoe, Japan, Japan

Department of Gastroenterology, Teikyo University Mizonokuchi Hospital

Kawasaki, Japan, Japan

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

Kobe, Japan, Japan

Department of Gastroenterology and Hepatology, Mie University Hospital

Mie, Japan, Japan

Department of Gastroenterology and Hepatology, Okayama University Hospital

Okayama, Japan, Japan

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

Osaka, Japan, Japan

Department of Gastroenterology and Hepatology, Kansai Medical University Medical Center

Osaka, Japan, Japan

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine

Osaka, Japan, Japan

Department of Gastroenterology, Shiga University of Medical Science

Shiga, Japan, Japan

Department of Gastroenterology, Tokyo Women's Medical University

Tokyo, Japan, Japan

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

Tokyo, Japan, Japan

Department of Gastroenterology, Wakayama Medical University School of Medicine

Wakayama, Japan, Japan

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

Aichi, Tokyo, Japan

Department of Gastroenterology, Nagoya University

Aichi, Tokyo, Japan

Department of Gastroenterology, The University of Tokyo Hospital

Bunkyō-Ku, Tokyo, Japan

Department of Gastroenterology, Graduate School of Medicine, Juntendo University

Bunkyō-Ku, Tokyo, Japan

Department of Gastroenterology, Fukuoka University

Fukuoka, Tokyo, Japan

Department of Gastroenterology, Kurume University

Fukuoka, Tokyo, Japan

Department of Gastroenterology, Matsunami General Hospital

Gifu, Tokyo, Japan

Department of Gastroenterology, Hiroshima University

Hiroshima, Tokyo, Japan

Department of Gastroenterology, JA Onomichi General Hospital

Hiroshima, Tokyo, Japan

Gastroenterology Center, Yokohama City University Medical Center

Kanagawa, Tokyo, Japan

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

Miyagi, Tokyo, Japan

Third Department of Internal Medicine, University of Toyama

Toyama, , Japan

Countries

Japan

Central Contacts

Yousuke Nakai

Role: CONTACT

ynakai-tky@umin.ac.jp

+81-3-3353-8111

Tomotaka Saito

Role: CONTACT

tomsaito-gi@umin.ac.jp

+81-3-3815-5411

Facility Contacts

Department of Gastroenterology, The University of Tokyo Hospit

Role: primary

Department of Gastroenterology, Graduate School of Medicine, J

Role: primary

Third Department of Internal Medicine, University of Toyama

Role: primary

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)

Other Identifiers

2025002P

Identifier Type: -

Identifier Source: org_study_id