INTRODUCTION: Sivelestat is neutrophil elastase inhibitor, which is widely used in Japan for the treatment of acute lung injury. However, the clinical efficacy of the medication has not been convincingly demonstrated. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials on sivelestat for the treatment of acute lung injury and acute respiratory distress syndrome. Studies were identified using MEDLINE, EMBASE, Cochrane library, conference proceedings, and references of included studies. Authors were contacted if necessary. ICHUSHI, the Japanese database for medical literature and conference proceedings was also used for the search, since many studies on sivelestat were published in Japanese language and not registered in major databases such as MEDLINE. The primary outcome was mortality within 28-30 days after randomization. Relative risks were pooled with the random effect model. RESULTS: 8 trials were included in the analysis. There was no difference in mortality within 28-30 days after randomization (relative risk 0.95, 95% confidence interval 0.72 to 1.26). Subgroup analysis conducted only on studies conducted in Japan showed the same result (0.59, 0.28 to 1.28). There was no difference in mechanical ventilation days (standardized mean difference -0.43, -1.12 to 0.27), but sivelestat was associated with a better short term PaO(2)/FiO(2) ratio (0.30, 0.05 to 0.56). Heterogeneity was not significant for the main analysis and funnel plot did not suggest publication bias. CONCLUSION: Sivelestat was not associated with decreased mortality, even when including studies published in Japanese language.
INTRODUCTION: Sivelestat is neutrophil elastase inhibitor, which is widely used in Japan for the treatment of acute lung injury. However, the clinical efficacy of the medication has not been convincingly demonstrated. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials on sivelestat for the treatment of acute lung injury and acute respiratory distress syndrome. Studies were identified using MEDLINE, EMBASE, Cochrane library, conference proceedings, and references of included studies. Authors were contacted if necessary. ICHUSHI, the Japanese database for medical literature and conference proceedings was also used for the search, since many studies on sivelestat were published in Japanese language and not registered in major databases such as MEDLINE. The primary outcome was mortality within 28-30 days after randomization. Relative risks were pooled with the random effect model. RESULTS: 8 trials were included in the analysis. There was no difference in mortality within 28-30 days after randomization (relative risk 0.95, 95% confidence interval 0.72 to 1.26). Subgroup analysis conducted only on studies conducted in Japan showed the same result (0.59, 0.28 to 1.28). There was no difference in mechanical ventilation days (standardized mean difference -0.43, -1.12 to 0.27), but sivelestat was associated with a better short term PaO(2)/FiO(2) ratio (0.30, 0.05 to 0.56). Heterogeneity was not significant for the main analysis and funnel plot did not suggest publication bias. CONCLUSION: Sivelestat was not associated with decreased mortality, even when including studies published in Japanese language.
Authors: Samira Saadoun; Patrick Waters; Claire MacDonald; B Anthony Bell; Angela Vincent; A S Verkman; Marios C Papadopoulos Journal: Ann Neurol Date: 2012-02-28 Impact factor: 10.422
Authors: Letizia Crocetti; Gianluca Bartolucci; Agostino Cilibrizzi; Maria Paola Giovannoni; Gabriella Guerrini; Antonella Iacovone; Marta Menicatti; Igor A Schepetkin; Andrei I Khlebnikov; Mark T Quinn; Claudia Vergelli Journal: Chem Cent J Date: 2017-12-06 Impact factor: 4.215
Authors: Nuala J Meyer; John P Reilly; Rui Feng; Jason D Christie; Stanley L Hazen; Carolyn J Albert; Jacob D Franke; Celine L Hartman; Jane McHowat; David A Ford Journal: JCI Insight Date: 2017-12-07