Efficacy and safety of ilaprazole for stress ulcer - associated upper gastrointestinal bleeding prophylaxis in critically ill patients: a randomized, double-blind, non-inferiority phase 3 trial.

Objectives: To evaluate the efficacy and safety of Ilaprazole in preventing stress ulcer-associated upper gastrointestinal bleeding in critically ill patients. Design: A Randomized, Double-Blind, non-inferiority Phase 3 Trial. Setting: 70 hospitals across China from July 16, 2021, to April 28, 2022. Patients: 441 Patients (mean age 59 years; 150 female) at high risk for stress ulcer bleeding requiring invasive mechanical ventilation were enrolled. Interventions: Patients were randomly assigned to receive either Ilaprazole (10 mg once daily, first dose doubled; 220 patients) or esomeprazole (40 mg twice daily; 221 patients). Measurements and main results: 441 patients (mean age 59 years; 150 female) were enrolled: 220 received Ilaprazole and 221 received esomeprazole. In FAS set, the primary endpoint occurred in 213 (96.80%) patients in the Ilaprazole and 215 (97.30%) in esomeprazole arms (Absolute Risk Difference: -0.47, 95% CI: -4.02, 3.03, p = 0.772). Secondary outcomes showed comparable incidences of clinically insignificant UGI bleeding, any gastrointestinal bleeding, 28-day mortality, ICU mortality, and pneumonitis. Adverse events were similar between groups, but Ilaprazole had a significantly lower incidence of hepatobiliary disorders (0.9% vs. 5%, p = 0.012). Conclusions: Ilaprazole demonstrated non-inferiority to esomeprazole in preventing UGI bleeding in critically ill patients at high risk of stress ulcer.