Immediate vs. On-demand Endoscopic Necrosectomy in Infected Walled-off Pancreatic Necrosis: A Randomized Controlled Trial

Endoscopic drainage is established treatment for infected walled-off pancreatic necrosis (WON). However, the optimal timing of necrosectomy remains controversial, with limited tier 1 evidence comparing immediate vs. on-demand necrosectomy strategies. This study compares the efficacy and safety of immediate versus on-demand endoscopic necrosectomy in patients with infected WON undergoing EUS-guided drainage. This is a single-center, prospective, randomized controlled superiority trial. Patients presenting with infected pancreatic necrosis were randomly assigned (1:1) to immediate necrosectomy or on-demand necrosectomy after initial EUS-guided drainage. Clinical success was defined as a reduction in the collection diameter to less than 3 cm, accompanied by complete resolution of the WON related symptoms. The primary outcome was the number of reinterventions to achieve clinical success. The secondary outcomes were procedure-related adverse events, length of hospital stay, necrosectomy procedure duration, and mortality. Between Sep 2022 and Dec 2024, we screened 84 patients, of whom 50 patients were randomly assigned to immediate necrosectomy (n=25) or on-demand necrosectomy (n=25). Baseline characteristics were similar between the 2 groups. Clinical success was achieved in 23 (92%) of the immediate and 22 (88%) of the on-demand necrosectomy patients (p=0.5). Median number of reinterventions was 1 (IQR: 0-2) in both groups [difference: – 0.16 (95% CI: – 0.42 to 0.1); p=0.5]. Median number of necrosectomy sessions, including the index procedure was 2 (IQR: 1-3) in the immediate necrosectomy, compared to 1 (IQR: 0-2) in the on-demand group [difference: – 0.44 (95% CI: – 0.63 to – 0.25); p= <0.01]. Forty four percent of the on-demand group resolved WON without necrosectomy. Procedure-related adverse events were 10 (40%) vs. 6 (24%) in the immediate and on-demand groups respectively [Relative risk: 1.67 (95% CI: 0.7 to 3.9); p= 0.2]. Moderate to severe adverse events occurred in 4 (16%) in the immediate necrosectomy as compared to none in the on-demand necrosectomy group [Relative risk: 0.84 (95% CI: 0.7 to 0.99); p= 0.1]. Major bleeding occurred in 2 (8%) of the immediate but in none of the on-demand group. Hospital stay (median 14 vs. 8 days; p=0.8) and mortality (8% vs. 12%; p=0.5) were similar between the 2 groups. In patients with infected walled-off pancreatic necrosis, immediate necrosectomy was not superior to on-demand necrosectomy. However, the on-demand strategy was associated with fewer necrosectomy sessions, and fewer adverse events. ClinicalTrials.gov number: NCT05530772