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

Not Applicable

Recruiting

• Conditions: Pancreatic Necrosis
• Interventions: Procedure: Endoscopic necrosectomy with direct approach; Procedure: Endoscopic necrosectomy with step up approach

• Registration Number: NCT05252897
• Lead Sponsor: Chinese University of Hong Kong

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.

Study Timeline

• Status Verified: 2022-02
• Study Start: 2022-02-01
• Study First Submitted: 2022-02-14
• Study First Submitted QC: 2022-02-14
• Last Update Submitted: 2022-02-22
• Study First Posted: 2022-02-23
• Last Update Posted: 2022-03-09
• Primary Completion: 2025-12-31
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 108

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%

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Direct endoscopic necrosectomy approach	Endoscopic necrosectomy with direct approach	Patients in the DEN group will undergo an immediate endoscopic necrosectomy after LAMS placement and balloon dilatation. A 10Fr 5cm double pigtail plastic stent will be inserted within the LAMS after necrosectomy. Patients will be assessed in 72 hours after the procedure. If there is no clinical improvement, a CECT is performed to check the adequacy of the drainage. DEN will be repeated in case of inadequate drainage. Patients will be reassessed every 72 hours and DEN repeated until there is clinical improvement. Subsequently, necrosectomy is performed weekly until a reassessment CECT at 3 weeks.
Endoscopic step-up approach	Endoscopic necrosectomy with step up approach	After endoscopic drainage of WON, patients will be reassessed 72 hours after the procedure. If there is no clinical improvement 72 hours after drain placement, a CECT is performed to check the adequacy of the drainage. Irrigation of the WON via a nasocystic drain or endoscopic irrigation (step 1) is performed in case of inadequate drainage. If a nasocystic drain is inserted, 500ml of normal saline, twice a day will be used to irrigate the WON. If endoscopic irrigation is performed, only irrigation with normal saline without necrosectomy is allowed. Patients are again evaluated 72 hours after step 1. In case of improvement, treatment is conservative; otherwise step 2 will be initiated, which is endoscopic necrosectomy. Further endoscopic necrosectomy will be performed until there is clinical improvement.

Primary Outcome Measures

Name	Time	Method
A composite of major complications or death within 6 months after randomisation	6 months	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

Secondary Outcome Measures

Name	Time	Method
Total ICU stay	6 months	No. of days for ICU stay
The individual components of the primary endpoint	6 months	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
Time to resolution of WOPN	6 months	LAMS insertion to LAMS removal
Exocrine pancreatic insufficiency	6 months	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
Biliary strictures	6 months	Presence of biliary strictures on cholangiogram/ CT/ MRI
Total no. of interventions	6 months	The total number of interventions including necrosectomy or other surgical/ radiological interventions
Length of hospital	6 months	The total length of hospital stay
Recurrence of WOPN	6 months	The recurrence of WOPN detected on imaging (CT/ USG/ MRI/ EUS)
Unplanned readmissions related to WOPN	6 months	The no. of unplanned readmissions related to WOPN
Endocrine pancreatic insufficiency	6 months	Insulin or oral antidiabetic drugs required 6 months after randomization; this requirement was not present before onset of acute pancreatitis
The no. of necrosectomies	6 months	The number of necrosectomies required

Trial Locations

Locations (9)

Asian Institute of Gastroenterology; 🇮🇳 Hyderabad, India

Deenanath Mangeshkar Hospital & Research Centre; 🇮🇳 Pune, India

Royal Adelaide Hospital; 🇦🇺 Adelaide, Australia

Medanta Institute Of Digestive & Hepatobiliary Sciences; 🇮🇳 Haryana, India

The Chinese University of Hong Kong; 🇭🇰 Hong Kong, Hong Kong

SoonChunHyang University School of Medicine; 🇰🇷 Asan, Korea, Republic of

Asan Medical Centre; 🇰🇷 Asan, Korea, Republic of

Hospital Universitario Rio Hortega; 🇪🇸 Valladolid, Spain

King Chulalongkorn Memorial Hospital; 🇹🇭 Bangkok, Thailand