Clinical trial NCT05252897: Timing of Necrosectomy After Endoscopic Drainage of Walled-off Pancreatic Necrosis (WON)
Official title: Direct Endoscopic Necrosectomy Versus Endoscopic Step-up Approach After Endoscopic Drainage of Walled-off Pancreatic Necrosis (WON)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Pancreatic Necrosis
Keywords: walled off pancreatic necrosis
endoscopic drainage
direct endoscopic necrosectomy
endoscopic step up approach
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2022-02-23
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomised controlled 2 arm trial
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: A composite of major complications or death within 6 months after randomisation
timeFrame: 6 months
Secondary outcomes:
measure: The individual components of the primary endpoint
timeFrame: 6 months
measure: Time to resolution of WOPN
timeFrame: 6 months
measure: Exocrine pancreatic insufficiency
timeFrame: 6 months
measure: Biliary strictures
timeFrame: 6 months
measure: Total no. of interventions
timeFrame: 6 months
measure: Length of hospital
timeFrame: 6 months
measure: Recurrence of WOPN
timeFrame: 6 months
measure: Unplanned readmissions related to WOPN
timeFrame: 6 months
measure: Endocrine pancreatic insufficiency
timeFrame: 6 months
measure: The no. of necrosectomies
timeFrame: 6 months
measure: Total ICU stay
timeFrame: 6 months
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Hong Kong
country: Hong Kong
facility: The Chinese University of Hong Kong
city: Haryana
country: India
facility: Medanta Institute Of Digestive & Hepatobiliary Sciences
city: Hyderabad
country: India
facility: Asian Institute of Gastroenterology
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital & Research Centre
city: Asan
country: Korea, Republic of
facility: Asan Medical Centre
city: Asan
country: Korea, Republic of
facility: SoonChunHyang University School of Medicine
city: Valladolid
country: Spain
facility: Hospital Universitario Rio Hortega
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital
Study officials:
References: