Prevention of upper gastrointestinal bleeding in critically ill Chinese patients: a randomized, double-blind study evaluating esomeprazole and cimetidine

Abstract

Objective: To assess the efficacy and safety of esomeprazole in preventing upper gastrointestinal (GI) bleeding in critically ill Chinese patients, using cimetidine as an active comparator.

Methods: A pre-specified non-inferiority limit (5%) was used to compare rates of significant upper GI bleeding in this randomized, double-blind, parallel-group, phase 3 study across 27 intensive care units in China. Secondary endpoints included safety and tolerability measures. Patients required mechanical ventilation and had at least one additional risk factor for stress ulcer bleeding. Patients were randomized to receive either active esomeprazole 40 mg, as a 30-min intravenous (IV) infusion twice daily, and an IV placebo cimetidine infusion or active cimetidine 50 mg/h, as a continuous infusion following an initial bolus of 300 mg, and placebo esomeprazole injections, given up to 14 days. Patients were blinded using this double-dummy technique.

Results: Of 274 patients, 2.7% with esomeprazole and 4.6% with cimetidine had significant upper GI bleeding (bright red blood in the gastric tube not clearing after lavage or persistent Gastroccult-positive “coffee grounds” material). Non-inferiority of esomeprazole to cimetidine was demonstrated. The safety profiles of both drugs were similar and as expected in critically ill patients.

Conclusions: Esomeprazole is effective in preventing upper GI bleeding in critically ill Chinese patients, as demonstrated by the non-inferiority analysis using cimetidine as an active control.

Trial registration: ClinicalTrials.gov identifier NCT02157376.

Keywords:

• Cimetidine
• Esomeprazole
• Gastrointestinal bleeding
• Mechanical ventilation
• Stress ulcer

This article is referred to by:

Upper gastrointestinal bleeding in critically ill patients: proton-pump inhibitors, histamine-2 receptor antagonists or placebo? Many questions remain unanswered

Transparency

Declaration of funding

This study was funded by AstraZeneca Gothenburg, Mölndal, Sweden.

Declaration of financial/other relationships

W.L., Y.X., P.X., L.Z., X.Y., and X.Q. have no conflicts to declare. S.L., H.R., and B.T. are employees of AstraZeneca and AstraZeneca shareholders. L.Z. and M.X. are employees of AstraZeneca. Peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no other relevant financial relationships to disclose.

Acknowledgments

Medical writing support was provided by Dr Nesta Hughes of Oxford PharmaGenesis, Oxford, UK, and was funded by AstraZeneca Gothenburg, Mölndal, Sweden. The editorial, manuscript revision, and resubmission support was provided by Advait Joshi, PhD, of Cactus Communications Pvt. Ltd.