Randomized Trial of Immediate Endoscopic Necrosectomy vs. Step-up Endoscopic Interventions in Necrotizing Pancreatitis

Study Overview
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Brief Summary
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This is a randomized trial comparing immediate endoscopic necrosectomy vs. step-up endoscopic interventions in patients with necrotizing pancreatitis.

Detailed Description
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In patients with necrotizing pancreatitis, there has been a recent shift away from surgical debridement (surgical necrosectomy) towards minimally invasive endoscopic treatment. Endoscopic management involves the creation of a fistula (tract) between the gastric or duodenal wall and the necrotic collection, under the guidance of endoscopic ultrasound (EUS) with subsequent placement of a stent. In addition, performing endoscopic necrosectomy, which involves extraction of necrotic material under direct endoscopic visualization has increased rates of treatment success to greater than 80%. However to date, there are currently scant data on the optimal timing of endoscopic necrosectomy. The aim of this randomized trial is therefore to compare the clinical outcomes between patients undergoing immediate endoscopic necrosectomy compared to step-up endoscopic interventions in patients undergoing endoscopic therapy for necrotizing pancreatitis.

Official Title
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Randomized Trial Comparing Immediate Endoscopic Necrosectomy vs. Step-up Endoscopic Interventions in Necrotizing Pancreatitis

Conditions
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Pancreatitis,Acute Necrotizing

Intervention / Treatment
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* Procedure: Immediate endoscopic necrosectomy
* Procedure: Step-up endoscopic interventions


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or over Symptomatic necrotic collection (that is suspected or confirmed to be infected), diagnosed on MRI or CT abdomen/pelvis (seen as a fluid collection in the setting of documented pancreatic necrosis that contains necrotic material and encased within a partial or complete wall) Necrotic collection of any size with extent to necrosis of ≥ 33% and any number of loculations, located within the pancreatic/peri-pancreatic space Necrotic collection visualized on EUS and amenable to EUS-guided drainage Exclusion Criteria: Age < 18 years Females who are pregnant Necrotic collection that is not amenable for EUS-guided drainage Irreversible coagulopathy (defined as INR >1.5, thrombocytopenia with platelet count < 50,000/mL) Use of anticoagulants that cannot be discontinued for the procedure Unable to obtain consent for the procedure from either the patient or LAR

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Immediate endoscopic necrosectomy<br>Endoscopic ultrasound (EUS)-guided drainage of the necrotic collection is performed using a lumen-apposing metal stent. Then in this group, endoscopic necrosectomy will be performed immediately following index EUS-guided drainage of the necrotic collection, during the same session | Procedure: Immediate endoscopic necrosectomy<br>* In the immediate endoscopic necrosectomy group, endoscopic ultrasound-guided drainage of the necrotic collection is performed using a lumen-apposing metal stent, immediately followed by endoscopic necrosectomy. Endoscopic necrosectomy involves removal of infected necrotic pancreatic tissue via the cystogastrostomy/cystoenterostomy tract using a variety of endoscopic accessories.<br>|
| Active Comparator: Step-up endoscopic intervention<br>Endoscopic ultrasound (EUS)-guided drainage of the necrotic collection is performed using a lumen-apposing metal stent. In this group, only EUS-guided drainage of the necrotic collection will be performed, and endoscopic necrosectomy will be performed at a separate session at a later time as needed. | Procedure: Step-up endoscopic interventions<br>* In the step-up endoscopic interventions group, endoscopic ultrasound-guided drainage of the necrotic collection is performed using a lumen-apposing metal stent. Endoscopic necrosectomy is not performed during the index drainage session, but is performed at a later time as needed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total number of reinterventions required for treatment success | Treatment success is defined as the resolution of necrotic collection on CT scan in association with clinical resolution of symptoms at 6-month follow-up (6 months from index intervention) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of treatment success | Treatment success is defined as the resolution of necrotic collection on CT scan in association with clinical resolution of symptoms at 6-month follow-up (6 months from index intervention) | 6 months | 
| Rate of resolution of pre-intervention systemic inflammatory response syndrome (SIRS) | Assessment of presence or absence of systemic inflammatory response syndrome prior to and 72 hours post intervention | 72 hours | 
| Rate of resolution of at least 1 pre-intervention organ failure at 72 hours post index intervention | Assessment of presence or absence of organ failure prior to and post intervention | 72 hours | 
| Total number of readmissions due to disease-related symptoms or procedure-related events | Assessment of readmissions due to disease-related or procedure-related events | 6 months | 
| Rate of technical success for EUS-guided cystogastrostomy | Technical success for EUS-guided cystogastrostomy is defined as the successful placement of the cystogastrostomy stent within the necrotic collection | 24 hours | 
| Rate of technical success for endoscopic necrosectomy | Technical success for endoscopic necrosectomy is defined as completion of endoscopic necrosectomy session as planned without the occurrence of adverse events | 24 hours | 
| Rate of exocrine pancreatic insufficiency | Exocrine pancreatic insufficiency is defined as fecal elastase level < 200μg/g in patients not previously taking pancreatic enzyme supplements | 6 months | 
| Rate of new onset diabetes | New onset diabetes is defined as new onset elevation in fasting plasma glucose ≥ 126 mg/dL, 2-hour plasma glucose ≥ 200 mg/dL after an oral glucose tolerance test or HbA1c ≥ 6.5% | 6 months | 
| Rate of procedure-related adverse events | Procedure-related adverse events is defined as any adverse event occurring as a result of any endoscopic intervention | 6 months | 
| Rate of disease-related adverse events | Disease-related adverse events is defined as any adverse event occurring as a result of necrotizing pancreatitis | 6 months | 
| Post-procedure length of intensive care unit (ICU) stay | Post-procedure length of intensive care unit (ICU) stay is defined as the number of days of patient's admission to the ICU following index intervention | 6 months | 
| Total length of hospital stay | Total length of hospital stay is defined as the number of days of patient's admission in the hospital following index intervention | 6 months | 
| Overall treatment costs measured in US dollars | Overall treatment costs include all relevant costs pertaining to treatment such as procedure costs, inpatient hospital stay costs, medication costs, materials costs, anesthesia costs, pharmacy costs and imaging studies costs. | 6 months |