A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis: ERASE

Yong-Hua Gao^{1

2

3}, Hai-Wen Lu^{1

2

3}, Hui-Zhen Zheng^{1

2

3}, Chao Cao⁴, De-Jie Chu⁵, Hong Fan⁶, Xiao-Yun Fan⁷, Hong-Yan Gu⁸, Wei-Jie Guan⁹, Zhi-Jun Jie¹⁰, Yang Jin¹¹, Wen Li¹², Yu-Ping Li¹³, Yuan-Yuan Li¹⁴, Lin Liu¹⁵, Xue-Dong Liu¹⁶, Hong Luo¹⁷, Xiao-Dong Lv¹⁸, Wei-Qiang Mo¹⁹, Yuan-Lin Song²⁰, Dao-Xin Wang²¹, Ling-Wei Wang²², Chang-Zheng Wang²³, Min Xie²⁴, Min Zhang²⁵, Cui-Xia Zheng²⁶, Bei Mao^{1

2}, Sanjay H Chotirmall^{27

28}, James D Chalmers^{29

30}, Jie-Ming Qu^{31

32

30}, Jin-Fu Xu^{1

2}

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
² Institute of Respiratory Medicine, School of Medicine, Tongji University, Shanghai, China.
³ These authors contributed equally as first authors.
⁴ Department of Respiratory Medicine, The Affiliated Hospital of School of Medicine, Ningbo University, Ningbo, China.
⁵ Department of Respiratory Medicine, The Eighth People's Hospital of Shanghai, Shanghai, China.
⁶ Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China.
⁷ Department of Geriatric Respiratory and Critical Care, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
⁸ Department of Pulmonary and Critical Care Medicine, The Sixth People's Hospital of Nantong, Nantong, China.
⁹ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
¹⁰ Department of Respiratory and Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.
¹¹ Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹² Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
¹³ Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
¹⁴ Department of Respiratory Medicine, Branch of National Clinical Research Center for Respiratory Disease, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
¹⁵ Department of Respiratory Medicine, Guizhou Provincial People Hospital, Guiyang City, China.
¹⁶ Tsingtao Municipal Hospital, Qingdao, China.
¹⁷ Department of Pulmonary and Critical Care Medicine, Second Xiangya Hospital, Central South University, Changsha, China.
¹⁸ Department of Respiration, The First Hospital of Jiaxing, Jiaxing, China.
¹⁹ Department of Respiration, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China.
²⁰ Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
²¹ Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
²² Pulmonary and Critical Care Department, Shenzhen People's Hospital, Shenzhen Institute of Respiratory Diseases, Shenzhen, China.
²³ Department of Respiratory Medicine, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
²⁴ Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
²⁵ Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
²⁶ Department of Respiratory Medicine, Shanghai Yangpu District Central Hospital, Tongji University, Shanghai, China.
²⁷ Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
²⁸ Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore, Singapore.
²⁹ Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK.
³⁰ These authors contributed equally as senior authors.
³¹ Department of Respiratory and Critical Care Medicine, Ruijin Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³² Institute of Respiratory Diseases, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

PMID: 38410702
PMCID: PMC10895435
DOI: 10.1183/23120541.00938-2023

A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis: ERASE

Yong-Hua Gao et al. ERJ Open Res. 2024.

. 2024 Feb 26;10(1):00938-2023.

doi: 10.1183/23120541.00938-2023. eCollection 2024 Jan.

Authors

Affiliations

¹ Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
² Institute of Respiratory Medicine, School of Medicine, Tongji University, Shanghai, China.
³ These authors contributed equally as first authors.
⁴ Department of Respiratory Medicine, The Affiliated Hospital of School of Medicine, Ningbo University, Ningbo, China.
⁵ Department of Respiratory Medicine, The Eighth People's Hospital of Shanghai, Shanghai, China.
⁶ Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China.
⁷ Department of Geriatric Respiratory and Critical Care, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
⁸ Department of Pulmonary and Critical Care Medicine, The Sixth People's Hospital of Nantong, Nantong, China.
⁹ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
¹⁰ Department of Respiratory and Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.
¹¹ Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹² Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
¹³ Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
¹⁴ Department of Respiratory Medicine, Branch of National Clinical Research Center for Respiratory Disease, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
¹⁵ Department of Respiratory Medicine, Guizhou Provincial People Hospital, Guiyang City, China.
¹⁶ Tsingtao Municipal Hospital, Qingdao, China.
¹⁷ Department of Pulmonary and Critical Care Medicine, Second Xiangya Hospital, Central South University, Changsha, China.
¹⁸ Department of Respiration, The First Hospital of Jiaxing, Jiaxing, China.
¹⁹ Department of Respiration, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China.
²⁰ Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
²¹ Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
²² Pulmonary and Critical Care Department, Shenzhen People's Hospital, Shenzhen Institute of Respiratory Diseases, Shenzhen, China.
²³ Department of Respiratory Medicine, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
²⁴ Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
²⁵ Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
²⁶ Department of Respiratory Medicine, Shanghai Yangpu District Central Hospital, Tongji University, Shanghai, China.
²⁷ Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
²⁸ Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore, Singapore.
²⁹ Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK.
³⁰ These authors contributed equally as senior authors.
³¹ Department of Respiratory and Critical Care Medicine, Ruijin Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, China.
³² Institute of Respiratory Diseases, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

PMID: 38410702
PMCID: PMC10895435
DOI: 10.1183/23120541.00938-2023

Abstract

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.

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Conflict of interest statement

Conflict of interest: W-J. Guan reports consulting fees from Joincare Pharmaceutical Co. Ltd., lecture fees from Joincare Pharmaceutical Co. Ltd., support for travel to attend domestic meetings from Joincare Pharmaceutical Co. Ltd., and is an associate editor of this journal. Conflict of interest: S.H. Chotirmall reports grants paid to his institution from the Singapore Ministry of Education, National Medical Research Council Singapore, consulting fees from CSL Behring, Pneumagen Ltd, Boehringer Ingelheim and Pneumagen Ltd, lecture fees from AstraZeneca and Chiesi, and participation in Data Safety and Monitoring Committees for Inovio Pharmaceuticals and Imam Abdulrahman Bin Faisal University. Conflict of interest: J.D. Chalmers reports grants from GSK, Boehringer Ingelheim, Genentech, Insmed, Grifols, Novartis, Gilead and AstraZeneca, consulting fees from AstraZeneca, Grifols, Genentech, GSK, Chiesi, Zambon, Trudell and Pfizer, and is an associate editor of this journal. Conflict of interest: J.F. Xu reports consulting fees from AstraZeneca and Boehringer Ingelheim. Conflict of interest: The remaining authors have nothing to disclose.

Figures

**FIGURE 1**
Study design. Usage and dosage of medications: ciprofloxacin 750 mg BD; ciprofloxacin placebo 750 mg BD; saline 5 mL BD; TIS 300 mg/5 mL BD. TIS: tobramycin inhalation solution.

See this image and copyright information in PMC

References

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A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis: ERASE

Affiliations

A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis: ERASE

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References