Skip to main content
OpenTrials
Recruiting

NCT Number: NCT05451901

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

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.

Recruiting

Interested in participating?

Request Info

Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Bunkyō-Ku, Tokyo, Japan

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Immediate necrosectomy

Procedure

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.

Step-up approach

Procedure

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).

Primary outcomes

  1. Time to clinical success from randomization

    Time frame: Six months

    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.

Secondary outcomes

  1. Adverse events

    Time frame: Five years

    All procedure-related adverse events including bleeding, perforation, peritonitis, etc.

  2. Mortality

    Time frame: Five years

    Mortality from any cause

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

    Time frame: One day

    Successful placement of EUS-guided drainage including a lumen-apposing metal stent and plastic stents

  4. Incidence of biliary and gastrointestinal stricture

    Time frame: Five years

    Inflammatory-induced obstruction of bile duct and gastrointestinal tract

  5. Number and time of interventions

    Time frame: Six months

    Total number of interventions and total procedure time

  6. Indwelling time of endoscopic and percutaneous drainage

    Time frame: Six months

    Indwelling period of stents and drainage tube

  7. Success rate and operation time of surgical procedures

    Time frame: Six months

    Success rate of surgeries associated with WON and total operation time

  8. Hospital stay and ICU stay

    Time frame: Six months

    Total hospitalization days and total ICU stay

  9. Duration of antibiotics administration

    Time frame: Six months

    Total administration days of antibiotics

  10. Cost of interventions and hospital stay

    Time frame: Six months

    Total cost of interventions and total cost of hospitalization

  11. Recurrence of WON

    Time frame: Five years

    Incidence of recurrence of WON

  12. Time to recurrence of WON

    Time frame: Five years

    Time from clinical success to recurrence of WON

  13. Treatment duration of recurrent WON

    Time frame: Five years

    Total treatment period for recurrent WON

  14. New onset of pseudocyst

    Time frame: Five years

    Incidence of new-onset pancreatic pseudocyst

  15. Treatment duration of new onset pseudocyst

    Time frame: Five years

    Total treatment period for new-onset pancreatic pseudocyst

  16. Incidence of new onset diabetes, clinical symptoms of pancreatic exocrine insufficiency, and pancreatic cancer

    Time frame: Five years

    New-onset diabetes mellitus, pancreatic cancer, and clinical symptoms associated with pancreatic exocrine insufficiency, such as steatorrhea , constipation, diarrhea, maldigestion, flatulence, and tenesmus

  17. The presence and timing of medications for pancreatic exocrine insufficiency

    Time frame: Five years

    The start of medications for pancreatic exocrine insufficiency and the date

  18. The presence and timing of sarcopenia

    Time frame: Five years

    The presence of sarcopenia and the date of diagnosis

  19. Morphological change of pancreas

    Time frame: Five years

    Change in the morphology and the volume of pancreas

Study contacts

Contact information is provided by the study sponsor or research team.

Tomotaka Saito

CONTACT

[email protected]

+81-3-3815-5411

Yousuke Nakai

CONTACT

[email protected]

+81-3-3815-5411

Sponsors and collaborators

Lead sponsor

Tokyo University

Other

Registry information

Official study title

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

Acronym: WONDER-01

Important dates

Study start
2022
Primary completion
2025
Study completion
2031
First posted
Jul 11, 2022
Registry last updated
Oct 27, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.