Sivelestat for Acute Respiratory Distress Syndrome Due to COVID-19

Study Overview
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Brief Summary
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A randomized, double-Blind, placebo-controlled trial aimed to investigate the safety and efficacy of sivelestat on treating adult patients with COVID-19-related acute respiratory distress syndrome (ARDS)

Detailed Description
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This study is designed as a randomized, double-blind, placebo-controlled clinical trial, and is planned to be conducted at 3 clinical centers in China from January 1, 2023, to January 31, 2024. During the study period, we intend to enroll a total of 238 eligible patients. These patients will be randomly assigned in a 1:1 ratio to receive either sivelestat sodium or placebo via continuous intravenous infusion (0.2mg/kg/h) over a 24-hour period for 7 days (or to the day of death or ICU discharge if it occurs before day 7). Both the patients and investigators are blinded to the treatment assignment. Subsequent follow-ups will be performed in person at 7,14 and 28 days after randomization. The primary endpoint will be at 7 days post randomization and secondary endpoints will be at 14 and 28 days post randomization. Also, endpoint assessors are masked to the treatment allocation. Lastly, these endpoint variables will be compared between the treatment groups to investigate the efficacy and safety of sivelestat for COVID-19-associated ARDS

Official Title
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Sivelestat for the Treatment of Adult Patients With Acute Respiratory Distress Syndrome Due to COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial

Conditions
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Respiratory Infection Virus, Respiratory Failure

Intervention / Treatment
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* Drug: Sivelestat Sodium for Injection
* Drug: The Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years old Confirmed SARS-CoV-2 infection as determined by Polymerase Chain Reaction (PCR) in sputum, nasopharyngeal swabs, or oropharyngeal swabs Diagnosis of acute respiratory distress syndrome (ARDS) according to the Berlin Definition criteria Onset of ARDS less than 72 hours before randomization Written informed consent Exclusion Criteria: ARDS potentially caused by extra-pulmonary reasons, including non-pulmonary sepsis, pancreatitis, multiple trauma and massive transfusion, etc. Leukopenia (leukocyte count <4,000/μL/) and/or thrombocytopenia (platelet count <100,000/μL) Significant hepatic dysfunction, defined as elevated AST and ALT ≥ 3 times the normal limits, or total bilirubin ≥ 1.5 mg/dL Severe renal insufficiency with serum creatinine > 3.0 mg/dL History of moderate to severe chronic lung disease requiring home-based oxygen therapy, including chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), asthma and bronchiectasis, etc. Pre-existing peripheral nerve injury, spinal cord trauma, or neuromuscular disorder that may impair spontaneous ventilation (e.g., high cervical spinal cord injury, Guillain-Barré Syndrome, and myasthenia gravis, etc.) Current diagnosis of pulmonary embolism Coexisting multi-organ failure, affecting more than 3 systems Combined with burn injury Life expectancy less than 6 months (e.g., due to an an end-stage malignant disease) Moribund and expected to die within 48 hours Known allergy to sivelestat or any of the study drug excipients Pregnancy or lactation, or the possibility of conception Current or recent (last 3 months) participation in any other clinical trial

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: the Sivelestat group<br>The patients in this group will receive sivelestat sodium via continuous intravenous infusion (0.2mg/kg/h) over a 24-hour period for 7 days | Drug: Sivelestat Sodium for Injection<br>* Sivelestat, a specific inhibitor of neutrophil elastase; sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenyl-sulfonylaminobenzoyl]amino-acetate tetrahydrate]<br>* Other names: Supportive management of ARDS (e.g., protective ventilation strategy, prone positioning and/or VV-ECMO, etc.) based on currently recommended practice guidelines;|
| Placebo Comparator: The Placebo group<br>The patients in this group will receive the placebo via continuous intravenous infusion (0.2mg/kg/h) over a 24-hour period for 7 days | Drug: The Placebo<br>* Excipients used for the sivelestat sodium<br>* Other names: Supportive management of ARDS (e.g., protective ventilation strategy, prone positioning and/or VV-ECMO, etc.) based on currently recommended practice guidelines;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PaO2/FiO2 ratio | Changes in the PaO2/FiO2 ratio | From randomization to day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilator-Free days | The number of Ventilator-Free Days | From randomization to day 28 | 
| In-hospital mortality | The rate of death during hospitalization | Through study completion, a period of 28 days | 
| Length of hospitalization | The overall length of hospital stay | Through study completion, a period of 28 days | 
| Intensive care unit (ICU) length of stay | The time interval between ICU admission and ICU discharge | Through study completion, a period of 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ARDS, COVID-19, Sivelestat, Randomized Trial