Protective Effect of Sivelestat Sodium on ARDS in Patients With Sepsis

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

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.

Study Overview

• Status: Recruiting
• Conditions: ARDS
• Intervention / Treatment: Drug: Sivelestat sodium; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Anticipated): 238
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Recruiting
      • Nanjing Zhong-Da Hospital, Southeast University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

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
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 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
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 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

Collaborators and Investigators

• Sponsor: Southeast University, China

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2021
• Primary Completion (Anticipated): September 30, 2023
• Study Completion (Anticipated): October 30, 2023

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: July 13, 2021
• First Posted (Actual): July 22, 2021

Study Record Updates

• Last Update Posted (Actual): April 5, 2023
• Last Update Submitted That Met QC Criteria: April 2, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: ARDS; efficacy; Sepsis; Respiratory Failure; Sivelestat sodium
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Sivelestat
• Other Study ID Numbers: ZDHL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No