Abstract
BACKGROUND: Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are life-threatening conditions with limited effective pharmacological interventions. Sivelestat sodium, a selective neutrophil elastase inhibitor, has been extensively investigated in ARDS/ALI treatment due to its significant anti-inflammatory properties; however, its therapeutic efficacy remains controversial. As a drug developed and first approved in Japan, most previous meta-analyses have failed to incorporate Japanese literature, potentially introducing substantial language bias. Additionally, Japanese clinical practices may employ different treatment protocols that could offer novel perspectives on sivelestat sodium's application. This systematic review aims to comprehensively evaluate sivelestat sodium's efficacy in ARDS/ALI patients by simultaneously including both English and Japanese clinical literature. METHODS: We will systematically search English databases (Cochrane Library, EMBASE, PubMed) and Japanese databases (Ichushi Web, J-STAGE) for randomized controlled trials comparing sivelestat sodium with placebo or standard therapy in adult ARDS/ALI patients. Two independent reviewers will screen studies, extract data, and assess risk of bias. Primary outcomes include duration of mechanical ventilation and all-cause mortality (28-30 days, ICU, and in-hospital). If sufficient eligible studies are identified, a random-effects model will be employed for meta-analysis. Between-study heterogeneity will be assessed using the I(2) statistic, and the certainty of evidence will be evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. DISCUSSION: This protocol outlines a systematic approach for evaluating sivelestat sodium's efficacy in ARDS/ALI through the integration of English and Japanese literature. Methodological rigor will ensure high-quality evidence synthesis despite challenges in integrating diverse studies. This research addresses a significant gap, as meta-analyses incorporating Japanese publications have been absent for over a decade. The findings will provide evidence-based guidance for clinical practice, inform individualized treatment strategies, optimize sivelestat administration protocols, and identify directions for future research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD420251067146.