Delayed bleeding (DB) after endoscopic mucosal resection (EMR) of large non-pedunculated colorectal lesions (LNPCL ≥20 mm) is a frequent clinically relevant adverse event in patients with intermediate–high bleeding risk according to the GSEED-RE2 score (≥4). Covergel® is a thermosensitive bioadhesive gel designed to seal post-EMR defects and may reduce bleeding risk. This interim analysis of the multicentre study COVER-PIC01-2023 evaluates the preliminary efficacy and safety of Covergel® for preventing DB after EMR of intermediate-high risk LNPCL.

This prospective, multicentre, single-arm investigation plans to enrol 121 patients. Adults with ≥1 LNPCL ≥20 mm and GSEED-RE2 ≥4 underwent complete EMR followed by uniform application of Covergel® using the Covercat® catheter. Adjunctive clip placement could be performed at the discretion of the endoscopist. Follow-up occurred at 24–72 h, 15 ± 3 days, and 30 ± 3 days. The primary endpoint was clinically relevant DB occurring >24 h and ≤30 days, defined as bleeding requiring hospitalisation, transfusion, therapeutic colonoscopy, radiological intervention, or surgery. Expected DB risk was calculated with the GSEED-RE2 model and compared with observed incidence using an exact one-sided binomial test. This interim analysis includes 69 consecutive patients with complete 30-day follow-up.

A total of 69 patients with ≥1 LNPCL ≥ 20 mm were analysed. The mean GSEED-RE2 score was 5.4 ± 1.4, corresponding to a mean predicted DB risk of 7.22% (range: 4.1–19.8%). Clips were placed in 39/69 patients (56.5%). Only one DB event occurred (1.45%), corresponding to an absolute risk reduction of 5.77% and a relative reduction of 79.9% compared with the expected risk; the reduction was statistically significant (exact binomial p≈0.04). The single DB episode occurred in a patient with GSEED-RE2 = 9 and no clip placement. No DB occurred in the Clip+Covergel subgroup (0/39), recognising that the study is not powered for between-group comparisons. No perforations, severe post-polypectomy syndrome, or device-related adverse events were identified.

Table 1. Summary of interim outcomes (n=69)

In this interim analysis, prophylactic application of Covergel® after EMR of intermediate-high risk LNPCL was associated with a significant reduction in delayed bleeding compared with GSEED-RE2–predicted risk and showed a favourable safety profile. The absence of delayed bleeding in patients treated with both Covergel® and selective clip placement is clinically promising, although not definitive in this non-comparative interim analysis. Recruitment is ongoing toward the target of 121 patients, and final results will be presented at ESGE Days 2026.