Timing of Necrosectomy After Endoscopic Drainage of Walled-off Pancreatic Necrosis (WON)

Pancreatic Necrosis Clinical Trial

Official title:

Direct Endoscopic Necrosectomy Versus Endoscopic Step-up Approach After Endoscopic Drainage of Walled-off Pancreatic Necrosis (WON)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05252897
• Other study ID #: 2021.465-T
• Status: Recruiting
• Phase: N/A
• Start date: February 1, 2022
• Est. completion date: June 30, 2026

Study information

• Verified date: February 2022
• Source: Chinese University of Hong Kong
• Contact: Shannon Chan
• Phone: 852-35052627
• Email: shannonchan[@]surgery.cuhk.edu.hk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: June 30, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Necrosis
• Pancreatic Necrosis
• Pancreatitis, Acute Necrotizing

Intervention

Procedure:
• Endoscopic necrosectomy with step up approach
Endoscopic necrosectomy will be performed with a forward-viewing gastroscope into the WON cavity. Debridement of necrotic tissue will be performed with irrigation and/or mechanical removal with endoscopic instruments. For this arm, step up approach will be adopted.
• Endoscopic necrosectomy with direct approach
Endoscopic necrosectomy will be performed with a forward-viewing gastroscope into the WON cavity. Debridement of necrotic tissue will be performed with irrigation and/or mechanical removal with endoscopic instruments. For this arm, the direct approach will be adopted.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Hong Kong	The Chinese University of Hong Kong	Hong Kong
India	Medanta Institute Of Digestive & Hepatobiliary Sciences	Haryana
India	Asian Institute of Gastroenterology	Hyderabad
India	Deenanath Mangeshkar Hospital & Research Centre	Pune
Korea, Republic of	Asan Medical Centre	Asan
Korea, Republic of	SoonChunHyang University School of Medicine	Asan
Spain	Hospital Universitario Rio Hortega	Valladolid
Thailand	King Chulalongkorn Memorial Hospital	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Chinese University of Hong Kong

Countries where clinical trial is conducted

Australia,  Hong Kong,  India,  Korea, Republic of,  Spain,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	A composite of major complications or death within 6 months after randomisation	Major complications include new onset multi-organ failure, multiple organ failure, persistent organ failure, bleeding requiring intervention, perforation of visceral organ requiring intervention, gas embolism	6 months
Secondary	The individual components of the primary endpoint	The individual components include new onset multi-organ failure, multiple organ failure, persistent organ failure, bleeding requiring intervention, perforation of visceral organ requiring intervention, gas embolism	6 months
Secondary	Time to resolution of WOPN	LAMS insertion to LAMS removal	6 months
Secondary	Exocrine pancreatic insufficiency	Exocrine pancreatic insufficiency defined as Oral pancreatic-enzyme supplementation required to treat clinical symptoms of steatorrhea 6 months after randomization; this requirement was not present before onset of acute pancreatitis	6 months
Secondary	Biliary strictures	Presence of biliary strictures on cholangiogram/ CT/ MRI	6 months
Secondary	Total no. of interventions	The total number of interventions including necrosectomy or other surgical/ radiological interventions	6 months
Secondary	Length of hospital	The total length of hospital stay	6 months
Secondary	Recurrence of WOPN	The recurrence of WOPN detected on imaging (CT/ USG/ MRI/ EUS)	6 months
Secondary	Unplanned readmissions related to WOPN	The no. of unplanned readmissions related to WOPN	6 months
Secondary	Endocrine pancreatic insufficiency	Insulin or oral antidiabetic drugs required 6 months after randomization; this requirement was not present before onset of acute pancreatitis	6 months
Secondary	The no. of necrosectomies	The number of necrosectomies required	6 months
Secondary	Total ICU stay	No. of days for ICU stay	6 months