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

Tokyo University

Status: Enrolling

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

Treatments: Procedure: Step-up approach; Procedure: Immediate necrosectomy

Study type: Interventional

Funder types: Other

Identifiers

NCT05451901

2021005P

jRCT1032220055 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 70 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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70 participants in 2 patient groups

Immediate necrosectomy

Experimental group

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.

Treatment:

Procedure: Immediate necrosectomy

Step-up approach

Active Comparator group

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.

Treatment:

Procedure: Step-up approach