Fexuprazan vs esomeprazole for endoscopic submucosal dissection-induced gastric ulcer healing: A double-blind randomized controlled trial

Figure 1 Study protocol. All patients received intravenous esomeprazole 40 mg twice daily for the first 2 days after endoscopic submucosal dissection (ESD). Beginning on post-ESD day 3, patients were assigned to receive either oral fexuprazan 40 mg/day plus placebo esomeprazole or oral esomeprazole 40 mg/day plus placebo fexuprazan, administered once daily before breakfast for 8 weeks. Follow-up assessments included laboratory testing on days 1, 3, and 14 and upper gastrointestinal endoscopy at 4 weeks and 8 weeks after ESD to evaluate ulcer healing status. ESD: Endoscopic submucosal dissection.

Figure 2 CONSORT flow diagram. Patients without an evaluable 8-week endoscopic assessment were imputed as treatment failures in the modified intention-to-treat and full intention-to-treat analyses; these patients were among those excluded from the per-protocol population and do not constitute an additional group. ESD: Endoscopic submucosal dissection.

Figure 3 Comparison of complete healing rates of the post-endoscopic submucosal dissection ulcer at 8 weeks. Complete healing at 8 weeks, the primary endpoint, was assessed by follow-up endoscopy and was defined as scar-stage healing (S1 or S2) without a residual mucosal defect according to the Sakita-Miwa classification. A: Per-protocol population (fexuprazan, n = 51; esomeprazole, n = 56): 46/51 (90.2%) vs 42/56 (75.0%); P = 0.040; B: Modified intention-to-treat population (n = 64 per group), in which patients without an evaluable 8-week assessment were classified as treatment failures: 47/64 (73.4%) vs 42/64 (65.6%); P = 0.337.

Figure 4 Exploratory analysis of the model-estimated time to a 99% reduction in ulcer area according to baseline ulcer area. In this per-protocol analysis, the time to a 99% reduction in ulcer area was estimated for each patient using an exponential decay model based on baseline and 4-week ulcer areas. A: Overall (40.31 days vs 47.22 days; P = 0.045); B: ≥ 800 mm² (42.89 days vs 47.62 days; P = 0.039); C: < 800 mm² (41.03 days vs 44.83 days; P = 0.588), shown for the fexuprazan vs esomeprazole groups. The curves are model-based extrapolations beyond the last observed measurement and do not represent observed times to endoscopic healing.