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Intravenous Esomeprazole for Prevention of Peptic Ulcer Rebleeding: A Randomized Trial in Chinese Patients

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Abstract

Introduction

High-dose intravenous esomeprazole is the only approved pharmacological treatment for the prevention of peptic ulcer rebleeding (currently approved in over 100 countries worldwide), but has not yet been approved in China. This study aimed to evaluate a high-dose esomeprazole intravenous regimen vs. an active control (cimetidine) for the prevention of rebleeding in Chinese patients with a high risk of peptic ulcer rebleeding who had undergone primary endoscopic hemostatic treatment.

Methods

This was a parallel-group study conducted at 20 centers in China. The study comprised a randomized, double-blind, intravenous treatment phase of 72 h in which 215 patients received either high-dose esomeprazole (80 mg + 8 mg/h) or cimetidine (200 mg + 60 mg/h), followed by an open-label oral treatment phase in which all patients received esomeprazole 40 mg tablets once daily for 27 days. The primary outcome was the rate of clinically significant rebleeding within the first 72 h after initial endoscopic hemostatic therapy. Secondary outcomes included the rates of clinically significant rebleeding within 7 and 30 days; proportions of patients who had endoscopic retreatment and other surgery due to rebleeding; and number of blood units transfused.

Results

The rate of clinically significant rebleeding within 72 h was low overall (3.3%) and numerically lower in patients treated with esomeprazole compared with cimetidine (0.9% vs. 5.6%). Overall, the results of the secondary outcomes also showed a numerical trend towards superiority of esomeprazole over cimetidine. All treatments were well tolerated.

Conclusion

In this phase 3, multicenter, randomized trial conducted in China, esomeprazole showed a numerical trend towards superior clinical benefit over cimetidine in the prevention of rebleeding in patients who had successfully undergone initial hemostatic therapy of a bleeding peptic ulcer, with a similar safety and tolerability profile. These findings suggest that esomeprazole may be an alternative treatment option to cimetidine for this indication in China.

Funding

AstraZeneca.

Trial registration

ClinicalTrials.gov identifier, NCT01757275.

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Acknowledgments

This study was funded by AstraZeneca. The article processing charges for this publication were funded by AstraZeneca Gothenburg, Mölndal, Sweden. Medical writing support was provided by Richard Claes (PhD) from Oxford PharmaGenesis, Oxford, UK, and was funded by AstraZeneca Gothenburg, Mölndal, Sweden. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. We thank the study participants, the study centers and the clinical teams of the Chinese Peptic Ulcer Bleeding Research Group, whose principal investigators are as follows: Zhao-Shen Li, Changhai Hospital, Shanghai; Min-Hu Chen, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou; Dong-Feng Chen, The Third Affiliated Hospital of the Third Military Medical University of PLA, Chongqing; Jiang Bo, Nanfang Hospital, Guangzhou; Feng Ji, The First Affiliated Hospital of Medicine School of Zhejiang University, Hangzhou; Wei-Hong Sha, Guangdong General Hospital, Guangzhou; You-Xiang Chen, The First Affiliated Hospital of Nanchang University, Nanchang; Xiao-Hua Hou, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan; De-An Tian, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan; Yong-Dong Wu, Beijing Friendship Hospital, Beijing; Lun-Gen Lu, Shanghai First People’s Hospital, Shanghai; Rong-Quan Wang, The First Affiliated Hospital of the Third Military Medical University of PLA, Chongqing; Yao-Zong Yuan, Shanghai Ruijin Hospital, Shanghai; Rui-Hua Shi, Jangsu Province People’s Hospital, Jiangsu General Hospital, Nanjing; Ji-Yong Liu, Shandong Province Hospital, Jinan; Yi-You Zou, Xiangya Hospital Central South University, Changsha; Shou-Rong Shen, The Third Xiangya Hospital of Central South University, Changsha; Kai-Chun Wu, Xijing Hospital, Xian; Xiao-Ping Zou, Nanjing Drum Tower Hospital, Nanjing; Bing-Rong Liu, The Second Hospital of Harbin Medical University, Harbin.

Disclosures

Yu Bai is supported by the 2014 Shanghai Rising-Star Program (A type, No. 14QA1404800) and Outstanding Young Scholars Fund of the Second Military Medical University, Shanghai. Huifang Chen is an employee of AstraZeneca. Stefan Eklund is an employee of AstraZeneca. Dong-Feng Chen, Rong-Quan Wang, You-Xiang Chen, Rui-Hua Shi, De-An Tian, and Zhao-Shen Li have no financial relationships to declare.

Compliance with ethics guidelines

All participants provided written informed consent. The study protocol was approved by the Shanghai Changhai Hospital Ethics Committee and the appropriate ethics committees for each center before the study began. The study was conducted in accordance with the Declaration of Helsinki, International Conference on Harmonization and Good Clinical Practice guidelines.

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China

    Yu Bai & Zhao-Shen Li

  2. Department of Gastroenterology, Daping Hospital, Third Military Medical University, Chongqing, China

    Dong-Feng Chen

  3. Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, China

    Rong-Quan Wang

  4. Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China

    You-Xiang Chen

  5. Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, China

    Rui-Hua Shi

  6. Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    De-An Tian

  7. AstraZeneca R&D, Shanghai, China

    Huifang Chen

  8. AstraZeneca Gothenburg, Mölndal, Sweden

    Stefan Eklund

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  1. Yu Bai
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  2. Dong-Feng Chen
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Corresponding author

Correspondence to Zhao-Shen Li.

Additional information

Y. Bai, D.-F. Chen, and R.-Q. Wang are co-first authors of this article.

On behalf of the Chinese Peptic Ulcer Bleeding Research Group.

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Bai, Y., Chen, DF., Wang, RQ. et al. Intravenous Esomeprazole for Prevention of Peptic Ulcer Rebleeding: A Randomized Trial in Chinese Patients. Adv Ther 32, 1160–1176 (2015). https://doi.org/10.1007/s12325-015-0265-6

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  • DOI: https://doi.org/10.1007/s12325-015-0265-6

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