China Launches Major Trial Testing Nafamostat Mesilate for Sepsis Treatment Across 32 Hospitals
核心洞察
The EASNMS trial is a multicenter, randomized, double-blind, placebo-controlled study recruiting 778 sepsis (搜索) patients across 32 ICUs in China to evaluate nafamostat mesilate's efficacy and safety.
Participants receive either continuous intravenous nafamostat mesilate at 2.0 mg/kg/day or placebo for seven days, with the primary endpoint being all-cause ICU mortality.
The study aims to address sepsis (搜索) mortality rates of 25-40% by targeting coagulation (搜索) activation, a key factor in progression to multiple organ dysfunction syndrome (搜索).
A large-scale clinical trial investigating nafamostat mesilate as a potential treatment for sepsis (搜索) has commenced across China, representing one of the most comprehensive efforts to evaluate anticoagulant therapy in critically ill patients. The EASNMS (Efficacy and Safety of Nafamostat Mesilate for Sepsis) study aims to recruit 778 patients from 32 intensive care units spanning 15 provinces.
Trial Design and Scope
The multicenter, randomized, double-blind, placebo-controlled trial addresses a critical medical need, given that sepsis (搜索) remains the leading cause of death in critically ill patients with in-hospital mortality rates of approximately 25-40%. The study protocol, approved by the Research and Ethics Committee of the First Affiliated Hospital of China Medical University (搜索), follows a 1:1 randomization design comparing nafamostat mesilate treatment against placebo.
Participants meeting Sepsis (搜索) 3.0 criteria will receive either continuous intravenous nafamostat mesilate at 2.0 mg/kg/day dissolved in 5% glucose solution or placebo consisting of glucose alone. Treatment continues for seven days, with enrollment required within six hours of ICU admission. The recruitment period extends from October 2023 to October 2025.
Scientific Rationale and Methodology
The trial's foundation rests on the understanding that coagulation (搜索) activation serves as an initial factor in sepsis (搜索) progression to multiple organ dysfunction syndrome (搜索) (MODS). This pathophysiological insight supports the potential benefit of anticoagulant therapy in sepsis management.
The study employs rigorous blinding procedures, with independent drug administrators at each center preparing identical-appearing 50-ml transparent syringes containing either nafamostat mesilate or glucose. Researchers, participants, and statisticians remain unaware of treatment allocation throughout the study period.
Primary and Secondary Endpoints
The primary outcome measures all-cause mortality in the ICU, analyzed using Cox proportional hazards models following intention-to-treat principles. Secondary endpoints encompass multiple clinically relevant parameters assessed over a 28-day follow-up period.
Key secondary outcomes include 28-day all-cause mortality, improvement in Sequential Organ Failure Assessment (SOFA) scores from baseline to days 3 and 7, and changes in Disseminated Intravascular Coagulation (搜索) (DIC) scores using both Japanese Association for Acute Medicine (JAAM) and International Society on Thrombosis and Hemostasis (ISTH) criteria. The study will also monitor adverse events, with particular attention to bleeding complications given nafamostat mesilate's anticoagulant properties.
Patient Population and Safety Measures
The trial targets adult patients meeting Sepsis (搜索) 3.0 criteria while implementing comprehensive exclusion criteria to ensure participant safety. Excluded patients include those under 18 years, pregnant or lactating women, and individuals with high bleeding risk or active bleeding conditions. The protocol also excludes patients who have received anticoagulant medications within specified timeframes before enrollment.
Safety monitoring includes systematic documentation of adverse events and serious adverse events throughout the 28-day study period. A Data Safety Monitoring Committee composed of clinicians, statisticians, ethicists, and legal advisors meets quarterly and on an ad hoc basis for emergency situations.
Statistical Considerations and Sample Size
The sample size calculation, based on literature estimates, assumes a 30% ICU mortality rate in the experimental group versus 40% in the control group. With one-sided alpha of 0.025 and beta of 0.2, the study requires 354 patients per group, totaling 708 cases. Accounting for a 10% dropout rate, the target enrollment reaches 778 participants.
The statistical analysis plan employs generalized linear mixed-effects models for SOFA and DIC score changes over time, while adverse event rates will be compared using chi-square or Fisher's exact tests. Missing data will be addressed through Multivariate Imputation by Chained Equations (MICE), with sensitivity analyses comparing imputed versus complete-case results.
Regulatory and Ethical Framework
The study operates under approval from the National Medical Products Administration of the People's Republic of China and adheres to International Council for Harmonisation Good Clinical Practice guidelines. The First Affiliated Hospital of China Medical University (搜索) serves as the trial sponsor, maintaining independence from study design, data collection, analysis, and reporting decisions.
Informed consent procedures accommodate patients with impaired decision-making capacity through legally authorized representatives, following Helsinki Declaration principles. Participants retain the right to withdraw at any time without negative consequences.
The EASNMS trial represents a significant investment in sepsis (搜索) research, potentially offering a new therapeutic approach for a condition with substantial mortality burden. If successful, nafamostat mesilate could provide clinicians with an additional treatment option to improve outcomes in critically ill sepsis patients across China and potentially globally.