Effects of intravenous sivelestat sodium on prevention of acute respiratory distress syndrome in patients with sepsis: study protocol for a double-blind multicentre randomised controlled trial
Introduction Sepsis is one of the most common risk factors for acute respiratory distress syndrome (ARDS). Neutrophil elastase (NE) is believed to be an important mediator of ARDS. When sepsis occurs, a large number of inflammatory factors are activated and released, which makes neutrophils migrate...
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| Format: | Article |
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BMJ Publishing Group
2023-09-01
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| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/13/9/e074756.full |
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| author | Zhiwei Gao Yi Yang Jianfeng Xie Haibo Qiu Cong Li Ling Liu Shaolei Ma |
| author_facet | Zhiwei Gao Yi Yang Jianfeng Xie Haibo Qiu Cong Li Ling Liu Shaolei Ma |
| author_sort | Zhiwei Gao |
| collection | DOAJ |
| description | Introduction Sepsis is one of the most common risk factors for acute respiratory distress syndrome (ARDS). Neutrophil elastase (NE) is believed to be an important mediator of ARDS. When sepsis occurs, a large number of inflammatory factors are activated and released, which makes neutrophils migrate into the lung, eventually leading to the occurrence of ARDS. Sivelestat sodium is an NE inhibitor that can inhibit the inflammatory reaction during systemic inflammatory response syndrome and alleviate lung injury. Therefore, we hypothesise that intravenous sivelestat sodium may prevent the occurrence of ARDS in patients with sepsis.Methods and analysis This is a prospective, investigator-initiated, double-blind, adaptive, multicentre, randomised, controlled clinical trial with an adaptive ‘sample size re-estimation’ design. Patients meeting the inclusion criteria who were transferred into the intensive care unit will be randomly assigned to receive sivelestat sodium or placebo for up to 7 days. The primary outcome is the development of ARDS within 7 days after randomisation. A total of 238 patients will be recruited based on a 15% decrease in the incidence of ARDS in the intervention group in this study. A predefined interim analysis will be performed to ensure that the calculation is reasonable after reaching 50% (120) of the planned sample size.Ethics and dissemination The study protocol was approved by the Ethics Committee of ZhongDa Hospital affiliated to Southeast University (identifier: Clinical Ethical Approval No. 2021ZDSYLL153-P03). Results will be submitted for publication in peer-reviewed journals and presented at relevant conferences and meetings.Trial registration number NCT04973670. |
| first_indexed | 2024-03-11T20:24:25Z |
| format | Article |
| id | doaj.art-90de64f76e3d4692a7ffd2610086fbc1 |
| institution | Directory Open Access Journal |
| issn | 2044-6055 |
| language | English |
| last_indexed | 2024-03-11T20:24:25Z |
| publishDate | 2023-09-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj.art-90de64f76e3d4692a7ffd2610086fbc12023-10-02T18:15:08ZengBMJ Publishing GroupBMJ Open2044-60552023-09-0113910.1136/bmjopen-2023-074756Effects of intravenous sivelestat sodium on prevention of acute respiratory distress syndrome in patients with sepsis: study protocol for a double-blind multicentre randomised controlled trialZhiwei Gao0Yi Yang1Jianfeng Xie2Haibo Qiu3Cong Li4Ling Liu5Shaolei Ma6Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, ChinaDepartment of Pediatric Endocrinology and Genetic Metabolism, Shanghai Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Yangpu, Shanghai, ChinaJiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, ChinaJiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, ChinaJiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, ChinaJiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, ChinaJiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, ChinaIntroduction Sepsis is one of the most common risk factors for acute respiratory distress syndrome (ARDS). Neutrophil elastase (NE) is believed to be an important mediator of ARDS. When sepsis occurs, a large number of inflammatory factors are activated and released, which makes neutrophils migrate into the lung, eventually leading to the occurrence of ARDS. Sivelestat sodium is an NE inhibitor that can inhibit the inflammatory reaction during systemic inflammatory response syndrome and alleviate lung injury. Therefore, we hypothesise that intravenous sivelestat sodium may prevent the occurrence of ARDS in patients with sepsis.Methods and analysis This is a prospective, investigator-initiated, double-blind, adaptive, multicentre, randomised, controlled clinical trial with an adaptive ‘sample size re-estimation’ design. Patients meeting the inclusion criteria who were transferred into the intensive care unit will be randomly assigned to receive sivelestat sodium or placebo for up to 7 days. The primary outcome is the development of ARDS within 7 days after randomisation. A total of 238 patients will be recruited based on a 15% decrease in the incidence of ARDS in the intervention group in this study. A predefined interim analysis will be performed to ensure that the calculation is reasonable after reaching 50% (120) of the planned sample size.Ethics and dissemination The study protocol was approved by the Ethics Committee of ZhongDa Hospital affiliated to Southeast University (identifier: Clinical Ethical Approval No. 2021ZDSYLL153-P03). Results will be submitted for publication in peer-reviewed journals and presented at relevant conferences and meetings.Trial registration number NCT04973670.https://bmjopen.bmj.com/content/13/9/e074756.full |
| spellingShingle | Zhiwei Gao Yi Yang Jianfeng Xie Haibo Qiu Cong Li Ling Liu Shaolei Ma Effects of intravenous sivelestat sodium on prevention of acute respiratory distress syndrome in patients with sepsis: study protocol for a double-blind multicentre randomised controlled trial BMJ Open |
| title | Effects of intravenous sivelestat sodium on prevention of acute respiratory distress syndrome in patients with sepsis: study protocol for a double-blind multicentre randomised controlled trial |
| title_full | Effects of intravenous sivelestat sodium on prevention of acute respiratory distress syndrome in patients with sepsis: study protocol for a double-blind multicentre randomised controlled trial |
| title_fullStr | Effects of intravenous sivelestat sodium on prevention of acute respiratory distress syndrome in patients with sepsis: study protocol for a double-blind multicentre randomised controlled trial |
| title_full_unstemmed | Effects of intravenous sivelestat sodium on prevention of acute respiratory distress syndrome in patients with sepsis: study protocol for a double-blind multicentre randomised controlled trial |
| title_short | Effects of intravenous sivelestat sodium on prevention of acute respiratory distress syndrome in patients with sepsis: study protocol for a double-blind multicentre randomised controlled trial |
| title_sort | effects of intravenous sivelestat sodium on prevention of acute respiratory distress syndrome in patients with sepsis study protocol for a double blind multicentre randomised controlled trial |
| url | https://bmjopen.bmj.com/content/13/9/e074756.full |
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