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

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

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

Asian Institute of Gastroenterology, India, West Virginia University, University of Southern California, Marshall University, Mayo Clinic, University of Alabama at Birmingham, Rush University

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

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.

Patient undergoing procedure and research coordinator assessing outcome measures during follow-up will be blinded to the treatment group to which the patients are randomized.

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

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.

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.

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.

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)

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)

Assessment of presence or absence of systemic inflammatory response syndrome prior to and 72 hours post intervention

Technical success for EUS-guided cystogastrostomy is defined as the successful placement of the cystogastrostomy stent within the necrotic collection

Technical success for endoscopic necrosectomy is defined as completion of endoscopic necrosectomy session as planned without the occurrence of adverse events

Exocrine pancreatic insufficiency is defined as fecal elastase level < 200μg/g in patients not previously taking pancreatic enzyme supplements

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%

Procedure-related adverse events is defined as any adverse event occurring as a result of any endoscopic intervention

Disease-related adverse events is defined as any adverse event occurring as a result of necrotizing pancreatitis

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

Total length of hospital stay is defined as the number of days of patient's admission in the hospital following index intervention

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.

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