Clinical trial NCT04113499: Endoscopic Necrosectomy Versus Step-up Endoscopic Intervention
Official title: A Randomized Trial Comparing Direct Endoscopic Necrosectomy vs. Step-up Transluminal Endoscopic Interventions in Infected Necrotizing Pancreatitis (DESTIN)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pancreatic Necrosis
Necrosis Pancreas
Keywords: pancreatic necrosis
pancreatic necrotic collection
transenteric drainage
necrosectomy
Lead sponsor: AdventHealth
Sponsor class: OTHER
First posted: 2019-10-02
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of treatment success
timeFrame: 6 months
Secondary outcomes:
measure: Rate of resolution of pre-intervention systemic inflammatory response syndrome
timeFrame: 72 hours post index procedure
measure: Rate of resolution of at least 1 pre-intervention organ failure
timeFrame: 72 hours post index procedure
measure: Number of re-admissions
timeFrame: 6 months
measure: Rate of technical success for EUS-guided cystogastrostomy
timeFrame: 24 hours
measure: Rate of technical success for endoscopic necrosectomy
timeFrame: 6 months
measure: Rate of exocrine pancreatic insufficiency
timeFrame: 6 months
measure: Rate of new onset diabetes
timeFrame: 6 months
measure: Number of Procedure-related adverse events
timeFrame: 6 months
measure: Number of Disease-related adverse events
timeFrame: 6 months
measure: Post-procedure length of intensive care unit (ICU) stay
timeFrame: 6 months
measure: Total length of hospital stay
timeFrame: 6 months
measure: Overall treatment costs
timeFrame: 6 months
Other outcomes:
Locations:
city: Orlando
country: United States
facility: Center for Interventional Endoscopy
state: Florida
Study officials:
affiliation: AdventHealth
name: Muhammad Hasan, MD
role: PRINCIPAL_INVESTIGATOR
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