Protective Effect of Sivelestat Sodium on ARDS in Patients With Sepsis

Study Overview
=================
Brief Summary
-----------------
Sivelestat sodium has been approved for use in patients with SIRS and ALI, but whether it can protect patients with sepsis from developing ARDS remains unknown.The aim of this study was to determine whether sivelestat sodium has a protective effect on ARDS in patients with sepsis.

Detailed Description
-----------------
The study was conducted in accordance with good clinical practice and with the guidelines set out in the Declaration of Helsinki. After approval from local and national ethics committees, patients from 3 centers in China were recruited. All patients were randomized, in a double-blind manner, to receive either sivelestat sodium regimen or a placebo regimen for 1- 7 days in ICU. The aim of this study was to determine whether sivelestat sodium has a protective effect on ARDS in patients with sepsis.

Official Title
-----------------
Protective Effect of Sivelestat Sodium on ARDS in Patients With Sepsis: Multicenter, Random, Double-blind, Parallel, Placebo Control Clinical Trials

Conditions
-----------------
ARDS

Intervention / Treatment
-----------------
* Drug: Sivelestat sodium
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Within 24 hours after admission, sepsis 3.0 diagnostic criteria were met; The patients or their family members fully understand the purpose and significance of the trial, voluntarily participate in the clinical trial, and sign the informed consent. Exclusion Criteria: Patients with ARDS were identified at the time of admission; Patients who explicitly refused mechanical ventilation; Patients with 3 or more extrapulmonary organ injuries and organ failure(single organ SOFA score ≥ 3); Patients who need home oxygen therapy or with home mechanical ventilation (by tracheotomy or noninvasive ventilation, but excluding CPAP / BiPAP, only for patients with obstructive sleep apnea); The patient whose expected survival time was less than 48 hours; Pregnant women and lactating women; Other conditions judged by the researcher not suitable for inclusion.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sivelestat sodium<br>Sivelestat sodium 0.2mg/kg.h | Drug: Sivelestat sodium<br>* Sivelestat sodium 0.2mg/kg.h for 1-7 days<br>|
| Active Comparator: placebo<br>The same amount of NS containing only sivelestat sodium excipients | Drug: Placebo<br>* The same amount of NS containing only sivelestat sodium excipients<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression to ARDS within 7 days (Berlin criteria) | The proportion of patients with sepsis progressing to ARDS | From study drug administration to days 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oxygenation index (PaO2/FiO2) or SpO2 / FiO2 on day 1, 3 and 7 from drug administration | PaO2/FiO2 or SpO2 / FiO2 was recorded on day 1, 3 and 7 from drug administration | From study drug administration to days 7 | 
| Concentration of inflammatory factors on day 1, 3 and 7 from drug administration | Inflammatory factors include Interleukin(IL)-1β,IL-6, IL-8, IL-10, tumor necrosis factor(TNF)-α | From study drug administration to days 7 | 
| Concentration of neutrophil elastase on day 1, 3 and 7 from drug administration | Concentration of neutrophil elastase was recorded on day 1, 3 and 7 from drug administration | From study drug administration to days 7 | 
| Platelet count on day 1, 3 and 7 from drug administration | Platelet count was recorded on day 1, 3 and 7 from drug administration | From study drug administration to days 7 | 
| Concentration of C-reactive protein on day 1, 3 and 7 from drug administration | Concentration of High sensitivity C-reactive protein was recorded on day 1, 3 and 7 from drug administration | From study drug administration to days 7 | 
| Sequential organ failure assessment (SOFA) score on day 1, 3 and 7 from drug administration | The SOFA scores on day 1, 3 and 7 were recorded | From study drug administration to days 7 | 
| The 28-day ventilator-free days (VFD) | Days alive and free from mechanical ventilation from study drug administration to day 28 | From study drug administration to day 28 | 
| The 28-day shock-free days | Days alive and free from vasopressor support which define as infusion of any vasopressor/inotrope agent for a minimum of 1 hour (i.e.norepinephrine, epinephrine, phenylephrine, vasopressin analogues, angiotensin, dopamine, dobutamine, milrinone or levosimendan) from study drug administration to day 28 | From study drug administration to day 28 | 
| The 28-day time to clinical improvement | Defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first. The seven-category ordinal scale consisted of the following categories: 1, not hospitalized with resumption of normal activities; 2, not hospitalized, but unable to resume normal activities; 3, hospitalized, not requiring supplemental oxygen; 4, hospitalized, requiring supplemental oxygen; 5, hospitalized, requiring nasal high-flow oxygen therapy, noninvasive mechanical ventilation, or both; 6, hospitalized, requiring ECMO, invasive mechanical ventilation, or both; and 7, death. | From study drug administration to day 28 | 
| Length of hospital stay | The number of days the subject stayed in the hospital | From administration to discharge hospital, up to 90 days | 
| The 28-day mortality | Death of any cause from study drug administration to day 28 | From study drug administration to day 28 | 
| The 90-day mortality | Death of any cause from study drug administration to day 90 | From study drug administration to day 90 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Sepsis, Respiratory Failure, ARDS, efficacy, Sivelestat sodium