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

Official title

Immediate Necrosectomy vs. Step-up Approach After EUS-guided Drainage of Walled-off Necrosis: a Multicenter Randomized Controlled Trial (WONDER-01)

Overview

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.

Interventions

• Procedure 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
• 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

Primary outcome measures

• Time to clinical success from randomization [Time frame: Six months]

Secondary outcome measures (12)

• Adverse events [Time frame: Five years]
• Mortality [Time frame: Five years]
• Technical success rate of initial EUS-PCD (Endoscopic ultrasonography-guided pseudocyst drainage) [Time frame: One day]
• Incidence of biliary and gastrointestinal stricture [Time frame: Five years]
• Number and time of interventions [Time frame: Six months]
• Indwelling time of endoscopic and percutaneous drainage [Time frame: Six months]
• Success rate and operation time of surgical procedures [Time frame: Six months]
• Hospital stay and ICU stay [Time frame: Six months]
• Duration of antibiotics administration [Time frame: Six months]
• Cost of interventions and hospital stay [Time frame: Six months]
• Recurrence of WON [Time frame: Five years]
• Time to recurrence of WON [Time frame: Five years]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Japan · 21 centers

• Department of Gastroenterology, The University of Tokyo Hospital — Bunkyō-Ku
• Department of Gastroenterology, Graduate School of Medicine, Juntendo University — Bunkyō-Ku
• Department of Gastroenterology, Aichi Medical University — Aichi
• Department of Gastroenterology, Graduate School of Medicine, Chiba University — Chiba
• Department of Gastroenterology, Gifu Municipal Hospital — Gifu
• Department of Gastroenterology, Gifu Prefectural General Medical Center — Gifu
• First Department of Internal Medicine, Gifu University Hospital — Gifu
• Division of Gastroenterology and Hepatobiliary and Pancreatic Diseases, Department of Inte — Hyōgo
• … and 13 more centers

Publications

• 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
• Saito T, Fujisawa T, Ogura T, Kuwatani M, Ohyama H, Takenaka M, Doi S, Iwata K, Hashimoto S, Kamada H, Iwashita T, Shiomi H, Masuda A, Matsubara S, Hayashi N, Maruta A, Kogure H, Inoue T, Yamada R, Shiratori T, Hamada T, Ueno S, Okuda A, Takahashi S, Sugiura R, Kawakubo K, Takahashi K, Kan M, Omoto S, Yamazaki T, Katsukura N, Okuno M, Hinokuchi M, Namima D, Uemura S, Nakano R, Sakai A, Suda K, Yos PMID 41720198
• 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 PMID 37226252

Identifiers

NCT: NCT05451901 · 2021005P · jRCT1032220055

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗