Endoscopic Necrosectomy Versus Step-up Endoscopic Intervention

Study Overview
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Brief Summary
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This trial is to compare clinical outcomes between patients undergoing immediate endoscopic necrosectomy compared to step-up endoscopic interventions in patients undergoing endoscopic therapy for infected necrotizing pancreatitis.

Detailed Description
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Acute pancreatitis has an annual incidence of 13-45 cases per 100,000 persons and is one of the most common gastrointestinal disorders requiring hospitalization worldwide. It leads to over a quarter of a million hospital admissions annually in the United States, and inpatient costs exceeding 2.5 billion US dollars. Pancreatic necrosis occurs as a consequence of severe acute pancreatitis in approximately 20% of patients. It can mature into a contained necrotic collection, typically four weeks into the disease course. With intense conservative management, including nutritional and intensive care support when required, the collection may resolve without intervention. However, a persistent collection with pain, gastric outlet, intestinal or biliary obstruction, new-onset or persisting organ failure, persistent unwellness or infection is associated with a mortality of 15-20%, and requires necrosectomy and drainage. Without intervention, infected necrosis ultimately leads to death in nearly every patient. Recently, there has been a shift away from surgical debridement (necrosectomy) towards minimally-invasive endoscopic methods in the treatment of necrotizing pancreatitis. Endoscopic management involves creation of a fistula between the enteric wall and necrotic collection under the guidance of endoscopic ultrasound [EUS] with subsequent placement of a stent to allow drainage of the necrotic material. Endoscopic transenteral drainage of necrotic collection is associated with favorable outcomes, with treatment success rates reported in the range of 45-70%. Endoscopic necrosectomy, with the additional technique of extraction of necrotic material under direct endoscopic visualization has increased rates of treatment success to greater than 80%. However, there are currently scant data on the optimal timing of endoscopic necrosectomy. In a retrospective study, performing endoscopic necrosectomy at the time of the initial EUS-guided drainage of the necrotic collection was associated with a significantly lower number of necrosectomy sessions compared to performing endoscopic necrosectomy one week after drainage. The aim of this randomized trial is to compare clinical outcomes between patients undergoing immediate endoscopic necrosectomy (direct endoscopic necrosectomy) compared to step-up endoscopic interventions in patients undergoing endoscopic therapy for infected necrotizing pancreatitis.

Official Title
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A Randomized Trial Comparing Direct Endoscopic Necrosectomy vs. Step-up Transluminal Endoscopic Interventions in Infected Necrotizing Pancreatitis (DESTIN)

Conditions
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Pancreatic Necrosis, Necrosis Pancreas

Intervention / Treatment
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* Procedure: Direct Endoscopic Intervention
* Procedure: Step-up Endoscopic Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject (or when applicable the subject's LAR) is capable of understanding and complying with protocol requirements The subject (or when applicable the subject's LAR) is able to understand and willing to sign an informed consent form prior to the initiation of any study procedures Males or females ≥ 18 years of age Necrotic collection 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 ≥ 33% of solid/necrotic component and any no. of loculations, located within the pancreatic/peri-pancreatic space Necrotic collection visualized on EUS and amenable to EUS-guided drainage Suspected/confirmed infected necrotic collection. Infected necrosis is defined by the presence of gas in the necrotic collection on cross-sectional imaging or positive culture of necrotic tissue obtained preprocedure or at first intervention. Infected necrosis is also suspected when sepsis is persistent or in the presence of ongoing clinical deterioration. Documented history of acute pancreatitis Acute pancreatitis is diagnosed if 2 of the following 3 criteria are met Abdominal pain characteristic of acute pancreatitis Serum lipase/amylase ≥ x3 upper limit of normal Characteristic radiological findings of acute pancreatitis on CECT/MRI/US abdomen, such as homogeneous enhancement of pancreatic parenchyma, standing of peripancreatic fat Able to undergo general anesthesia Exclusion Criteria: Females who are pregnant or lactating. Pregnancy for females of childbearing potential will be determined by routine preoperative urine or serum HCG testing. Irreversible coagulopathy (INR >1.5, thrombocytopenia with platelet count <50,000/mL) Has surgically altered gastrointestinal anatomy such as but not limited to Billroth II, Roux-en-Y, gastric bypass Age < 18 years Unable to obtain consent for the procedure from either the patient or LAR Use of anticoagulants that cannot be discontinued for the procedure Unable to tolerate general anesthesia Necrotic collection that is not accessible for EUS-guided drainage Percutaneous drainage of the necrotic collection is required or performed prior to EUS-guided drainage

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Direct Endoscopic Necrosectomy<br>The subject will have endoscopic drainage and necrosectomy at the time of the index intervention. | Procedure: Direct Endoscopic Intervention<br>* The necrotic collection is first identified using a linear echoendoscope. A Hot AXIOS stent is utilized in all patients for EUS-guided drainage of the necrotic collection. The necrotic material is sent for gram stain and culture with sensitivities. For endoscopic necrosectomy, in patients allocated to direct endoscopic necrosectomy group, endoscopic necrosectomy is performed during the same session as the index endoscopic drainage. It is performed using a therapeutic gastroscope and various accessories (see below for further details) for 90 to 120 minutes.<br>|
| Active Comparator: Step-up Endoscopic Interventions<br>The subject will only have endoscopic drainage of the pancreatic necrotic collection at the time of index intervention. | Procedure: Step-up Endoscopic Intervention<br>* The necrotic collection is first identified using a linear echoendoscope. A Hot AXIOS stent is utilized in all patients for EUS-guided drainage of the necrotic collection. The necrotic material is sent for gram stain and culture with sensitivities. In patients allocated to the step-up endoscopic interventions group, endoscopic necrosectomy is not performed at the time of the index intervention, however it is performed when clinically indicated during the follow-up period (6 months from index intervention).<br>|

What is the study measuring?
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Primary 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of resolution of pre-intervention systemic inflammatory response syndrome | Assessment of preintervention systemic inflammatory response syndrome & their resolution and measured by yes/no. | 72 hours post index procedure | 
| Rate of resolution of at least 1 pre-intervention organ failure | Assessment of organ failure following the index procedure and their resolution and measured by yes/no. | 72 hours post index procedure | 
| Number of re-admissions | Assessing the total number of re-admissions following the index procedure. | 6 months | 
| Rate of technical success for EUS-guided cystogastrostomy | Technical success for EUS-guided cystogastrostomy defined as completion of endoscopic necrosectomy session as planned without the occurrence of adverse events and measured by yes/no. | 24 hours | 
| Rate of technical success for endoscopic necrosectomy | Technical success for endoscopic necrosectomy defined as any adverse event occurring as a result of necrotizing pancreatitis and measured by yes/no. | 6 months | 
| Rate of exocrine pancreatic insufficiency | Rate of exocrine pancreatic insufficiency defined as fecal elastase level < 200μg/g in patients not previously taking pancreatic enzyme supplements | 6 months | 
| Rate of new onset diabetes | Rate of new onset diabetes 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 | 
| Number of Procedure-related adverse events | Procedure-related adverse events defined as any adverse event occurring as a result of any endoscopic intervention. The subject will be asked to report and medical records will be reviewed for any adverse events related to the procedure. | 6 months | 
| Number of Disease-related adverse events | Disease-related adverse events, defined as any adverse event occurring as a result of necrotizing pancreatitis. The subject will be asked to report and medical records will be reviewed for any adverse events related to the procedure. | 6 months | 
| Post-procedure length of intensive care unit (ICU) stay | Measured in the number of days in the intensive care unit | 6 months | 
| Total length of hospital stay | Measured in the number of days in the hospital | 6 months | 
| Overall treatment costs | Overall treatment costs from admission until 6 months post index intervention. All relevant costs pertaining to treatment will be taken into consideration - procedure costs, inpatient hospital stay from date of procedure to discharge, readmissions, medications, materials, anesthesia, pharmacy and imaging studies. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic necrosis, pancreatic necrotic collection, transenteric drainage, necrosectomy