Immediate vs. On-demand Endoscopic Necrosectomy in Infected Walled-off Pancreatic Necrosis

Study Overview
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Brief Summary
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Acute pancreatitis is one of the most common diagnoses made in gastroenterology wards worldwide which causes a great deal of pain and expense along with fatal complications. Approximately, 10-20% of patients progress to necrotizing pancreatitis that result in significant morbidity and mortality. Initial conservative management may be feasible in necrotizing pancreatitis, however the majority of patients with infected necrosis or persistent symptoms will eventually require a drainage procedure. Drainage procedures for necrotizing pancreatitis include open surgery, minimally invasive surgery, percutaneous drainage, and endoscopic drainage. In the recent years, minimally invasive approaches have largely replaced open surgical necrosectomy. Endoscopic drainage of walled off pancreatic necrosis involves creation of a transmural fistula between the enteral lumen and WOPN cavity with stent placement under endoscopic ultrasound (EUS) guidance. Furthermore, direct endoscopic necrosectomy can be performed through the fistula track. The best timing for endoscopic necrosectomy is not yet defined. A recent retrospective study suggested that immediate necrosectomy after stent placement results in earlier resolution of WOPN with fewer sessions of endoscopic necrosectomy. The aim of this study is to compare immediate vs. on-demand endoscopic necrosectomy in patients with infected WOPN who undergo EUS-guided transmural drainage of WOPN.

Detailed Description
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Acute pancreatitis is one of the most common diagnoses made in gastroenterology wards worldwide which causes a great deal of pain and expense along with fatal complications (1). The incidence of acute pancreatitis is trending upward in the United States with $2.6 billion annual health care costs (2). While most patients present with mild and interstitial form of pancreatitis, 10-20% of patients progress to necrotizing pancreatitis that result in significant morbidity and mortality (3). Initial conservative management may be feasible in necrotizing pancreatitis (4), however the majority of patients with infected necrosis or persistent symptoms will eventually require a drainage procedure (5). Drainage procedures for necrotizing pancreatitis include open surgery, minimally invasive surgery, percutaneous drainage, and endoscopic drainage. Drainage procedures are typically postponed for several weeks until the necrotic cavity becomes walled off which is called walled off pancreatic necrosis (WOPN). In the recent years, minimally invasive approaches have largely replaced open surgical necrosectomy (6). Endoscopic drainage of walled off pancreatic necrosis involves creation of a transmural fistula between the enteral lumen and WOPN cavity with stent placement under endoscopic ultrasound (EUS) guidance. Furthermore, direct endoscopic necrosectomy can be performed through the fistula track. The best timing for endoscopic necrosectomy is not yet defined. A recent retrospective study suggested that immediate necrosectomy after stent placement results in earlier resolution of WOPN with fewer sessions of endoscopic necrosectomy (7). The aim of this study is to compare immediate vs. on-demand endoscopic necrosectomy in patients with infected WOPN who undergo EUS-guided transmural drainage of WOPN. Infected necrosis is diagnosed with one of the following criteria in patients with WOPN three weeks after onset of acute pancreatitis (8): A. Positive Gram's stain or culture from a fine-needle aspiration; B. the presence of gas within pancreatic and peripancreatic necrosis on contrast-enhanced CT scan; C. Presence of two inflammatory variables (temperature >38.5°C or elevated C-reactive protein levels or leukocyte counts) in the absence of another focus of infection (other than infected necrosis) ; D. Presence of persistent organ failure.

Official Title
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Immediate Endoscopic Necrosectomy vs. On-demand Necroectomy in Infected Walled-off Pancreatic Necrosis

Conditions
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Pancreatitis, Acute Necrotizing

Intervention / Treatment
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* Device: Endoscopic necrosectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented history of acute pancreatitis Necrotic collection with partial or complete wall diagnosed on CT or MRI Necrotic collection of any size with any number of loculations with more than 20% of solid/necrotic component Necrotic collection is accessible and amenable for EUS-guided drainage Age >= 18 years Suspected or confirmed infection in the necrotic collection The patient understands and accepts to sign the informed consent. Exclusion Criteria: Irreversible coagulopathy with INR>1.5 or platelet counts <50,000 Necrotic collection is not accessible for EUS-guided drainage Females who are pregnant Previous intervention (e,g, percutaneous drainage, or surgery) is performed for the patient

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immediate endoscopic Necrosectomy<br>The subject will have endoscopic necrosectomy at the time of the EUS-guided transmural stent placement. The necrotic collection is identified with endoscopic ultrasonography (EUS). Transmural placement of stent under EUS guidance is performed. The type of stent is at the discretion of endoscopist. It could be either lumen apposing metallic stent or double pigtail plastic stent. Immediately after stent placement, the cystoenterostomy track is dilated with a 15 mm through the scope (TTS) balloon. Then, direct endoscopic necrosectomy is performed with CO2 insufflation. The duration of necrosectomy will be 30 to 90 minutes. If complete clearance of the cavity is achieved before 30 minutes, the duration of necrosectomy may be less than 30 minutes in the given session. Also, if any complication occurs during necrosectomy, appropriate management will be done, and the procedure may be concluded earlier. | Device: Endoscopic necrosectomy<br>* Initially, a tract is created between the stomach or duodenum with the walled-off pancreatic necrotic collection through placement of a stent. Then, the endosocpe is entered the necrotic cavity with CO2 insufflation, and the necrotic materials are removed with snare, grasper, or suctioning.<br>|
| Active Comparator: On-demand endoscopic necrosectomy<br>The subject will have EUS-guided transmural drainage of the necrotic collection The necrotic collection is identified with endoscopic ultrasonography (EUS). Transmural placement of stent under EUS guidance is performed. The type of stent is at the discretion of endoscopist. It could be either lumen apposing metallic stent or double pigtail plastic stent. In this group, endoscopic necrosectomy is not performed at the time of index procedure. Such patients may undergo endoscopic necrosectomy during follow up if clinically indicated. | Device: Endoscopic necrosectomy<br>* Initially, a tract is created between the stomach or duodenum with the walled-off pancreatic necrotic collection through placement of a stent. Then, the endosocpe is entered the necrotic cavity with CO2 insufflation, and the necrotic materials are removed with snare, grasper, or suctioning.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical success rate | Clinical success rate is compared between the two groups. Clinical success is defined as complete resolution of WOPN without residual fluid component along with resolution of symptoms three months after stent placement | Three months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| procedure-related adverse events | Comparing procedure-related adverse events between the two groups. Adverse events including bleeding, perforation, secondary infection are compared. | Three months | 
| Length of hospital stay | Comparing length of hospital stay between the two groups. Total length of hospital stay is recorded and compared. | Three months | 
| Number of necrosectomy sessions | Comparing number of necrosectomy sessions between the two groups | Three months | 
| Total duration of necrosectomies (in miniute) | Comparing total duration of necrosectomies (in miniute) between the two groups. Total duration of necrosectomies (in miniute) in all necroectomy sessions is recorded and compared between the two groups. | Three months | 
| Rate of new onset diabetes mellitus | Comparing rate of new onset diabetes mellitus between the two groups | Three months | 
| Mortality rate | Comparing mortality rate between the two groups | Three months | 
| Number of patients requiring surgery | Comparing number of patients requiring surgery between the two groups | Three months |