Accelerated vs Step-Up Endoscopic Treatment for Pancreatic Walled-Off Necrosis: A Randomized Controlled Trial (ACCELERATE)

Endoscopic step-up treatment with ultrasound-guided drainage and necrosectomy has become the gold standard treatment of pancreatic walled-off necrosis (WON); however, the length of stay (LOS) in hospital of patients with large WON remains substantial. We hypothesized that an accelerated treatment protocol could reduce LOS and major complications in patients with large WON. This single-center, open-label, randomized controlled trial conducted at a tertiary care facility in Denmark included patients with WON >15 cm, randomized to either an accelerated or step-up treatment approach. In the accelerated group, necrosectomy was performed during the index procedure and repeated as needed. In the step-up group, necrosectomy was only performed in cases without clinical improvement. The primary composite endpoints were death, major complications, and LOS >58 days. The trial, which was prematurely terminated due to concerns of the safety of the patients in the step-up group based on a benefit-to-risk assessment, included 25 patients (12 accelerated, 13 step-up). Baseline characteristics were comparable between groups. The primary composite outcome occurred in 8.3% of patients in the accelerated group versus 61.5% in the step-up group (absolute risk reduction 53.5%, RR 0.14; p=0.011). Major complications occurred less frequently in the accelerated group (0.0% vs. 46.2%; p=0.015), and median LOS was shorter (32.5 days [Q1-Q3: 17.5-38.2] vs. 68.5 days [Q1-Q3: 35.5-97.8]; p=0.039). An accelerated treatment protocol may significantly reduce the risk of major complications, the LOS, and the inflammatory burden compared to a step-up approach, suggesting its adoption in treatment large WON. (ClinicalTrials.gov, Number NCT05601687).