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

RECRUITING

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.

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Study details:

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.

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Eligibility criteria

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Inclusion criteria

Adult (≥18 years of age) patients

Diagnosis of walled-off pancreatic necrosis (WON) based on imaging criteria based on the revised Atlanta classification5

Documented history of acute pancreatitis

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*

WON identified at contrast-enhanced computed tomography (CECT) and deemed amenable for EUS-guided drainage

WON with a solid component >30% and/ or percentage of necrosis >= 30%

Exclusion criteria

Previous invasive interventions for necrotising pancreatitis

An acute flare up of chronic pancreatitis

Recurrent acute pancreatitis

Indicated for emergency laparotomy (i.e. abdominal compartment syndrome, perforation of a visceral organ, bleeding and bowel ischaemia)

Contraindications to endoscopic drainage: previous total gastrectomy, gastric bypass surgery, prior surgery for pancreas-related diseases

WON not adherent to the GI wall or not accessible for endoscopic drainage

Coagulopathy (INR >1.5), and/or thrombocytopenia (platelets <50,000/mm3)

Pregnancy

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2022-02-01

Primary completion: 2025-12-31

Study completion finish: 2026-06-30

Study type

TREATMENT

Phase

Trial ID

NCT05252897

Intervention or treatment

PROCEDURE: Endoscopic necrosectomy with step up approach

PROCEDURE: Endoscopic necrosectomy with direct approach

Conditions

• Pancreatic Necrosis

Condition: Pancreatic Necrosis
PROCEDURE: Endoscopic necrosectomy with step up approach and other drugs
Adelaide, Not Specified, Australia
Sponsor: Chinese University of Hong Kong

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Closest Location:

Royal Adelaide Hospital

Research sites nearby

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Royal Adelaide Hospital
Adelaide, Not Specified, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
ACTIVE_COMPARATOR: Endoscopic 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.	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.
ACTIVE_COMPARATOR: Direct endoscopic necrosectomy 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.	PROCEDURE: 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.

Participant Group/Arm

Intervention/Treatment

ACTIVE_COMPARATOR: Endoscopic 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.

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.

ACTIVE_COMPARATOR: Direct endoscopic necrosectomy 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.

PROCEDURE: 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.

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
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 outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
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
Time to resolution of WOPN	LAMS insertion to LAMS removal	6 months
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
Biliary strictures	Presence of biliary strictures on cholangiogram/ CT/ MRI	6 months
Total no. of interventions	The total number of interventions including necrosectomy or other surgical/ radiological interventions	6 months
Length of hospital	The total length of hospital stay	6 months
Recurrence of WOPN	The recurrence of WOPN detected on imaging (CT/ USG/ MRI/ EUS)	6 months
Unplanned readmissions related to WOPN	The no. of unplanned readmissions related to WOPN	6 months
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
The no. of necrosectomies	The number of necrosectomies required	6 months
Total ICU stay	No. of days for ICU stay	6 months

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References

Clinical Trials Gov: Timing of Necrosectomy After Endoscopic Drainage of Walled-off Pancreatic Necrosis (WON)