Endoscopic Necrosectomy Versus Step-up Endoscopic Intervention

Not Applicable

Completed

• Conditions: Pancreatic Necrosis; Necrosis Pancreas
• Interventions: Procedure: Step-up Endoscopic Intervention; Procedure: Direct Endoscopic Intervention

• Registration Number: NCT04113499
• Lead Sponsor: AdventHealth

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2019-10-01
• Study First Submitted QC: 2019-10-01
• Study First Posted: 2019-10-02
• Study Start: 2019-11-27
• Primary Completion: 2022-04-25
• Study Completion: 2022-04-25
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-11
• Last Update Posted: 2023-07-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

Inclusion Criteria

1. The subject (or when applicable the subject's LAR) is capable of understanding and complying with protocol requirements

2. 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

3. Males or females ≥ 18 years of age

4. 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)

5. Necrotic collection of any size with ≥ 33% of solid/necrotic component and any no. of loculations, located within the pancreatic/peri-pancreatic space

6. Necrotic collection visualized on EUS and amenable to EUS-guided drainage

7. 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.

8. Documented history of acute pancreatitis Acute pancreatitis is diagnosed if 2 of the following 3 criteria are met

   1. Abdominal pain characteristic of acute pancreatitis
   2. Serum lipase/amylase ≥ x3 upper limit of normal
   3. Characteristic radiological findings of acute pancreatitis on CECT/MRI/US abdomen, such as homogeneous enhancement of pancreatic parenchyma, standing of peripancreatic fat

9. Able to undergo general anesthesia

Exclusion Criteria

1. Females who are pregnant or lactating. Pregnancy for females of childbearing potential will be determined by routine preoperative urine or serum HCG testing.
2. Irreversible coagulopathy (INR >1.5, thrombocytopenia with platelet count <50,000/mL)
3. Has surgically altered gastrointestinal anatomy such as but not limited to Billroth II, Roux-en-Y, gastric bypass
4. Age < 18 years
5. Unable to obtain consent for the procedure from either the patient or LAR
6. Use of anticoagulants that cannot be discontinued for the procedure
7. Unable to tolerate general anesthesia
8. Necrotic collection that is not accessible for EUS-guided drainage
9. Percutaneous drainage of the necrotic collection is required or performed prior to EUS-guided drainage

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Step-up Endoscopic Interventions	Step-up Endoscopic Intervention	The subject will only have endoscopic drainage of the pancreatic necrotic collection at the time of index intervention.
Direct Endoscopic Necrosectomy	Direct Endoscopic Intervention	The subject will have endoscopic drainage and necrosectomy at the time of the index intervention.

Primary Outcome Measures

Name	Time	Method
Rate of treatment success	6 months	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

Secondary Outcome Measures

Name	Time	Method
Rate of technical success for endoscopic necrosectomy	6 months	Technical success for endoscopic necrosectomy defined as any adverse event occurring as a result of necrotizing pancreatitis and measured by yes/no.
Number of Disease-related adverse events	6 months	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.
Post-procedure length of intensive care unit (ICU) stay	6 months	Measured in the number of days in the intensive care unit
Overall treatment costs	6 months	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.
Rate of new onset diabetes	6 months	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%
Number of Procedure-related adverse events	6 months	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.
Rate of technical success for EUS-guided cystogastrostomy	24 hours	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.
Rate of exocrine pancreatic insufficiency	6 months	Rate of exocrine pancreatic insufficiency defined as fecal elastase level \< 200μg/g in patients not previously taking pancreatic enzyme supplements
Rate of resolution of pre-intervention systemic inflammatory response syndrome	72 hours post index procedure	Assessment of preintervention systemic inflammatory response syndrome \& their resolution and measured by yes/no.
Rate of resolution of at least 1 pre-intervention organ failure	72 hours post index procedure	Assessment of organ failure following the index procedure and their resolution and measured by yes/no.
Number of re-admissions	6 months	Assessing the total number of re-admissions following the index procedure.
Total length of hospital stay	6 months	Measured in the number of days in the hospital

Trial Locations

Locations (1)

Center for Interventional Endoscopy; 🇺🇸 Orlando, Florida, United States