Immediate Necrosectomy vs. Step-up Approach for Walled-off Necrosis
- Conditions
- Pancreatic PseudocystPancreatic Fluid CollectionPancreatitis, Acute NecrotizingWalled-off Necrosis
- Interventions
- Procedure: Immediate necrosectomyProcedure: Step-up approach
- Registration Number
- NCT05451901
- Lead Sponsor
- Tokyo University
- Brief Summary
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 70
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Immediate necrosectomy Immediate necrosectomy 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. Step-up approach Step-up approach 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.
- Primary Outcome Measures
Name Time Method Time to clinical success from randomization 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 Outcome Measures
Name Time Method Number and time of interventions Six months Total number of interventions and total procedure time
Recurrence of WON Five years Incidence of recurrence of WON
Treatment duration of recurrent WON Five years Total treatment period for recurrent WON
The presence and timing of sarcopenia Five years The presence of sarcopenia and the date of diagnosis
Technical success rate of initial EUS-PCD (Endoscopic ultrasonography-guided pseudocyst drainage) One day Successful placement of EUS-guided drainage including a lumen-apposing metal stent and plastic stents
Incidence of biliary and gastrointestinal stricture Five years Inflammatory-induced obstruction of bile duct and gastrointestinal tract
Indwelling time of endoscopic and percutaneous drainage Six months Indwelling period of stents and drainage tube
Duration of antibiotics administration Six months Total administration days of antibiotics
Treatment duration of new onset pseudocyst Five years Total treatment period for new-onset pancreatic pseudocyst
Cost of interventions and hospital stay Six months Total cost of interventions and total cost of hospitalization
Incidence of new onset diabetes, clinical symptoms of pancreatic exocrine insufficiency, and pancreatic cancer 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
The presence and timing of medications for pancreatic exocrine insufficiency Five years The start of medications for pancreatic exocrine insufficiency and the date
Adverse events Five years All procedure-related adverse events including bleeding, perforation, peritonitis, etc.
Mortality Five years Mortality from any cause
Time to recurrence of WON Five years Time from clinical success to recurrence of WON
New onset of pseudocyst Five years Incidence of new-onset pancreatic pseudocyst
Morphological change of pancreas Five years Change in the morphology and the volume of pancreas
Success rate and operation time of surgical procedures Six months Success rate of surgeries associated with WON and total operation time
Hospital stay and ICU stay Six months Total hospitalization days and total ICU stay
Trial Locations
- Locations (21)
Department of Gastroenterology, The University of Tokyo Hospital
🇯🇵Bunkyō-Ku, Tokyo, Japan
Department of Gastroenterology, Aichi Medical University
🇯🇵Aichi, Japan
Department of Gastroenterological Endoscopy, Kanazawa Medical University
🇯🇵Kanazawa, Japan
Department of Gastroenterology, Graduate School of Medicine, Juntendo University
🇯🇵Bunkyō-Ku, Tokyo, Japan
First Department of Internal Medicine, Gifu University Hospital
🇯🇵Gifu, Japan
Division of Gastroenterology and Hepatobiliary and Pancreatic Diseases, Department of Internal Medicine, Hyogo Medical University
🇯🇵Hyōgo, Japan
Department of Gastroenterology, Gifu Prefectural General Medical Center
🇯🇵Gifu, Japan
Department of Gastroenterology, Gifu Municipal Hospital
🇯🇵Gifu, Japan
Department of Gastroenterology, Graduate School of Medicine, Chiba University
🇯🇵Chiba, Japan
Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University
🇯🇵Kagawa, Japan
Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences
🇯🇵Kagoshima, Japan
Department of Gastroenterology, Kameda Medical Center
🇯🇵Kamogawa, Japan
Department of Gastroenterology and Hepatology, Saitama Medical Center, Saitama Medical University
🇯🇵Kawagoe, Japan
Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine
🇯🇵Kobe, Japan
Department of Gastroenterology, Teikyo University Mizonokuchi Hospital
🇯🇵Kawasaki, Japan
Department of Gastroenterology, Yuuai Medical Center
🇯🇵Okinawa, Japan
2nd Department of Internal Medicine, Osaka Medical College
🇯🇵Osaka, Japan
Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine
🇯🇵Tokyo, Japan
Third Department of Internal Medicine, University of Toyama
🇯🇵Toyama, Japan
Department of Gastroenterology and Hepatology, Hokkaido University Hospital
🇯🇵Sapporo, Japan
Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine
🇯🇵Ōsaka-sayama, Japan