Walled-off pancreatic necrosis (WON) is associated with a mortality of 20-30%. The current evidence supports a minimally invasive drainage approach to infected WON. The current suggested approach in international guidelines is the endoscopic step-up approach. However, recent evidence from large national cohorts support the use of direct endoscopic necrosectomy (DEN) at the time of stent placement, resulting in earlier resolution of WON and less number of necrosectomies. This study aims to investigate the clinical outcomes of the DEN versus the step-up approach for necrosectomy after endoscopic drainage of WON.

INTRODUCTION Acute pancreatitis is one of the most common gastrointestinal diseases requiring emergency admissions to the hospital. 10-20% of these patients develop pancreatic necrosis and subsequent walled-off pancreatic necrosis (WON) and is associated with a mortality of 20-30%. Grade 1A evidence exists to support an initial minimally invasive drainage approach to infected WON. However, the optimal approach and timing of necrosectomy remains unaddressed. The current suggested approach in international guidelines is the endoscopic step-up approach. However, recent evidence from large national cohorts support the use of direct endoscopic necrosectomy (DEN) at the time of stent placement, resulting in earlier resolution of WON and less number of necrosectomies.

OBJECTIVE This study aims to investigate the clinical outcomes of the DEN versus the step-up approach for necrosectomy after endoscopic drainage of WON.

HYPOTHESIS The hypothesis is that DEN at the time of LAMS placement improves clinical outcomes after endoscopic drainage of WON as compared to the endoscopic step-up approach.

DESIGN AND SUBJECTS This is a multicentre international randomized controlled trial. Patients with suspected or confirmed infected or symptomatic WON on computed tomography (CT) and who are deemed feasible for endoscopic drainage will be included in the study. Endoscopic drainage with lumen-apposing metal stents (LAMS) will be performed. Patients will be randomised to either the endoscopic step-up approach or direct endoscopic necrosectomy (DEN) approach.

The primary endpoint is a composite of major complications or death within 6 months after randomisation. Secondary endpoints include time to resolution of WON, pancreatic functions, biliary strictures, need for necrosectomy, total number of interventions, length of hospital and ICU stay, recurrence of WON and unplanned readmissions related to WON.

A reduction in cumulative primary endpoint with the DEN approach by 22.4% (32.2% to 9.8%) in comparison to endoscopic step-up approach was assumed. With a 2-sided significance level of 5% and power of 80%, taking into account a 5% drop-out rate, a total of 108 patients was required to demonstrate this effect. Study collaboration has been established with four other international centres. A estimation of 3 years is required to complete study recruitment.

Inclusion Criteria:

1. Adult (≥18 years of age) patients
2. Diagnosis of walled-off pancreatic necrosis (WON) based on imaging criteria based on the revised Atlanta classification5
3. Documented history of acute pancreatitis
4. Suspected or confirmed infected WON and/or symptomatic WON causing (i) persistent pancreatic-type pain, and/or ii) gastric outlet or biliary obstruction, and/or (iii) ongoing systemic illness, anorexia, and weight loss, and/or (iv) rapidly enlarging WONs, and/or (v) infected WON*
5. WON identified at contrast-enhanced computed tomography (CECT) and deemed amenable for EUS-guided drainage
6. WON with a solid component >30% and/ or percentage of necrosis >= 30%

Exclusion Criteria:

1. Previous invasive interventions for necrotising pancreatitis
2. An acute flare up of chronic pancreatitis
3. Recurrent acute pancreatitis
4. Indicated for emergency laparotomy (i.e. abdominal compartment syndrome, perforation of a visceral organ, bleeding and bowel ischaemia)
5. Contraindications to endoscopic drainage: previous total gastrectomy, gastric bypass surgery, prior surgery for pancreas-related diseases
6. WON not adherent to the GI wall or not accessible for endoscopic drainage
7. Coagulopathy (INR >1.5), and/or thrombocytopenia (platelets <50,000/mm3)
8. Pregnancy