A Randomized Clinical Trial To Assess The Efficacy And Safety Of Esomeprazole For Treatment Of Acute Non-variceal Upper Gastrointestinal Bleeding

OBJECTIVE:The objective of this study is to evaluate the efficacy of Esomeprazole infusion in subjects with acute non-variceal upper gastrointestinal bleeding. The study is performed in order to meet the regulatory requirements for the indication of treatment of non-variceal upper GI bleeding using Esomeprazole.METHOD:The study is carried out as a multi-center, randomized, double-blind, double dummy, parallel-group, active-controlled non-inferiority study to assess the efficacy and safety of Esomeprazole 40 mg q12h infusion or Omeprazole 40 mg q12h infusion for 5 days in subjects with acute non-variceal upper gastrointestinal bleeding. It is conducted in 13 SFDA certified gastrointestinal department. Totally 448 patients with acute non-variceal upper gastrointestinal bleeding, verified by endoscopies at baseline was randomised.RESULT:The primary endpoint, the proportion of no clinically significant upper gastrointestinal bleeding after 5 days treatment, exceeded 95% in both treatment groups in ITT population, with 95.3% and 97.2% in Esomeprazole group and Omeprazole group respectively. Esomeprazole group is non- inferior to Omeprazole group in subjects with acute non-variceal upper gastrointestinal bleeding. (p=0.3699) Compared with ITT population, the result in PP population was similar with 97.1% vs 98% in Esomeprazole and Omeprazole treatment groups respectively (p=0.6297).In terms of second efficacy results, no statistical significant differences were shown between two treatment groups. After 72 hours treatment, the proportion of no clinically significant upper gastrointestinal bleeding in Esomeprazole and Omeprazole group were 87.2% and 90.8 respectively (p=0.3146). The median time to absence of clinically significant upper gastrointestinal bleeding was same with 48 hours in both treatment groups (p=0.4161). One subject in Omeprazole group was needed surgery during the treatment period, while none in Esomeprazole group had this need (p=0.244). The median numbers of transfused blood units in Esomeprazole and Omeprazole group were 400 ml and 300 ml, respectively within both 5 days (p=0.1591) and 3 days (p=0.2127).CONCLUSION:In both ITT and PP population, the proportion of no clinically significant upper gastrointestinal bleeding after 5-day treatment in Esomeprazole group was non-inferior to Omeprazole group in subjects with acute non-variceal upper gastrointestinal bleeding, and exceeded 95% in both treatment groups. Adverse events were evenly distributed across the treatment groups and both drugs were well tolerated.