Nafamostat Mesilate in the Treatment of Severe Infection-associated Coagulopathy

Study Overview
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Brief Summary
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The objective of this study was to evaluate the therapeutic effect of nafamostat mesilate on patients with severe infection-related coagulation。

Official Title
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Nafamostat Mesilate in the Treatment of Severe Infection-associated Coagulopathy: a Multicenter Randomized Controlled Trial

Conditions
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Sepsis, Sepsis-induced Coagulopathy, Nafamostat Mesilate

Intervention / Treatment
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* Drug: Nafamostat mesilate
* Drug: 5% glucose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: meets the criteria for sepsis 3.0. Targeted population for SIC anticoagulant therapy（http://research-kudo-prediction.s3-website-ap-northeast-1.amazonaws.com/） Exclusion Criteria: Age less than 18, pregnant women, and lactating women Patients with a history of hypersensitivity to nafamostat mesilate (previous use of nafamostat mesilate resulted in significant bleeding complications) Fibrinogen < 1.5g/L Patients with bleeding or high bleeding risk Patients in the acute phase of trauma or with active bleeding (such as flail chest, significant contusions of the lungs, liver, kidneys, spleen, retroperitoneal bleeding, pelvic fractures, etc.) History of severe traumatic brain injury, intracranial surgery, stroke, cerebral aneurysm, or arteriovenous malformation within the past month prior to enrollment Patients with a history of congenital bleeding disorders (such as hemophilia) Patients with underlying fulminant hepatitis, decompensated cirrhosis, or other severe liver diseases Patients receiving the following medications Patients who have received heparin and heparin analogs (including low molecular weight heparin, dalteparin, etc.) within the past 12 hours prior to treatment Patients who have received warfarin within the past 7 days prior to the study and have an INR level above normal Patients who have undergone thrombolytic therapy within the past 3 days prior to the study Patients who have received platelet inhibitors (such as aspirin, clopidogrel, ticlopidine, dipyridamole, etc.) within the past 7 days prior to the study Patients currently receiving other novel anticoagulant medications (such as Xa factor inhibitors like apixaban, rivaroxaban, edoxaban, etc., direct thrombin inhibitors like dabigatran ICU treatment time is expected to be no more than 24h Patients who have undergone cardiopulmonary resuscitation within the past 7 days prior to the study Patients who have participated in other studies within the 30 days prior to enrollment Due to irreversible disease states, such as advanced malignant tumors or other end-stage diseases; or patients in a terminal state deemed by the physician to be approaching death

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Nafamostat mesilate treatment group (experimental group) : Basic treatment + Nafamostat mesilate 2.0 mg/kg/d Placebo control group: Basic treatment + 5% glucose with Nafamostat mesilate equal volume
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo control group<br> | Drug: 5% glucose<br>* Add 50ml of 5% glucose into a 50ml syringe<br>|
| Experimental: Nafamostat mesilate treatment group (experimental group)<br> | Drug: Nafamostat mesilate<br>* Nafamostat mesilate treatment group was dissolved with 5% glucose at the dosage of 2.0mg/kg/ day to a total of 50ml(Maximum concentration 10mg/ml)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality in ICU |  | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in organ function (SOFA score) |  | 7 days | 
| DIC score (JAAM/ISTH score) changes; |  | 7 days | 
| 28-day all-cause fatality rate |  | 28-day | 
| Adverse event rate |  | 7 days |