Treatment of ARDS With Sivelestat Sodium (TOAWSS)

Efficacy of Sivelestat Sodium in the Treatment of ARDS With SIRS, a Multicenter Double-blind Randomized Controlled Clinical Trial

Neutrophil elastase (NE) released by neutrophils play an important role in inflammatory cascade and lung tissue injury of ARDS.Inhibition of NE is expected to prevent the pathophysiological process of ARDS and alleviate lung injury. Siverestat sodium is a specific inhibitor of NE, which has been proved by basic and observational clinical studies to be effective in alleviating lung injury of ARDS, but there is a lack of prospective multi-center randomized controlled clinical trials.Therefore, this study was intended to evaluate the efficacy of sivelestat sodium in the treatment of ARDS patients with SIRS in a multicenter randomized controlled clinical trial

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: Saline; Drug: Sivelestat sodium

• Study Type: Interventional
• Enrollment (Actual): 324
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Sichuan Privince
    • Chengdu, Sichuan Privince, China
      • Sichuan Provincial People's Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Males and females > 18 years old and <75 years old (non-pregnant, non-lactating females).
2. Patients fulfilled the Berlin diagnostic criteria of acute respiratory distress syndrome, with a arterial oxygen partial pressure (PaO2) to fraction of inspired oxygen (FiO2) between 150 mmHg and 300 mmHg.
3. Signed written informed consent has been obtained

Exclusion Criteria:

1. History of chronic respiratory disease
2. Single cardiogenic pulmonary edema
3. Apach2 score ≥21 points
4. Complicated with end-stage disease, or poor prognosis judged by the clinical doctor in charge
5. ARDS course>3 days
6. Agranulocytosis or receiving immunosuppressive agents or high doses of corticosteroids (methylprednisolone>40mg/day)
7. Pregnancy or breastfeeding
8. Participated in this study
9. Do not agree to participate in this experiment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: Saline	Drug: Saline; 50ml normal saline was continuously pumped in the dark for 24h. Applied for 5 consecutive days
Experimental: Sivelestat Sodium	Drug: Sivelestat sodium; 4.8mg/kg sivelestat sodium was given in 50ml normal saline, and was continuously pumped in the dark for 24h, equivalent to 0.2mg/kg/h.Applied for 5 consecutive days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
oxygenation improvement rate	day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Invasive mechanical ventilation rate		day 28
length of stay in ICU		day 28
length of stay in hospital		day 28
28 days mortality		day 28
ICU mortality		day 28
Incidence of acquired infections		day 28
oxygenation improvement rate		day 1
oxygenation improvement rate		day 5
incidence of severe adverse effect		day 28
activity of neutrophil elastase in plasma		day0
activity of neutrophil elastase in plasma		day 1
activity of neutrophil elastase in plasma		day 3
activity of neutrophil elastase in plasma		day 5
concentration of IL-6		day 0
concentration of IL-6		day 1
concentration of IL-6		day 3
concentration of IL-6		day 5
concentration of IL-10		day 0
concentration of IL-10		day 1
concentration of IL-10		day 3
concentration of IL-10		day 5
28-day ventilator-free days	The 28-day VFDs is defined as the number of study days that the patient is alive and off mechanical ventilation after successful weaning. If a patient dies within 28 days, the VFD is recorded as 0.	day 28

Collaborators and Investigators

• Sponsor: Sichuan Provincial People's Hospital
• Investigators: Principal Investigator: Xiaobo Huang, MD, Sichuan Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2022
• Primary Completion (Actual): September 13, 2025
• Study Completion (Actual): October 6, 2025

Study Registration Dates

• First Submitted: May 20, 2021
• First Submitted That Met QC Criteria: May 26, 2021
• First Posted (Actual): June 2, 2021

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Acute Respiratory Distress Syndrome
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Respiratory Distress Syndrome; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; Sodium Chloride
• Other Study ID Numbers: SichuanPPHospital

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentifed individual participant data are available after the article is published. Data can be accessed with the approval of the authors. Request for data can be made to the corresponding author (drhuangxb@163.com and panchun1982@gmail.com) and will be discussed during a meeting including investigators from all paticipating centers
• IPD Sharing Time Frame: Deidentifed individual participant data are available after the article is published.
• IPD Sharing Access Criteria: Data can be accessed with the approval of the authors. Request for data can be made to the corresponding author (drhuangxb@163.com and panchun1982@gmail.com) and will be discussed during a meeting including investigators from all paticipating centers
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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