Sivelestat for Acute Respiratory Distress Syndrome Due to COVID-19

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

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)

Study Overview

• Status: Not yet recruiting
• Conditions: Respiratory Failure; Respiratory Infection Virus
• Intervention / Treatment: Drug: Sivelestat Sodium for Injection; Drug: The Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 238
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jingwei Zhao, M.D.; Phone Number: 86-010-59975098; Email: 126-zjw@163.com
• Study Contact Backup: Name: Bin Zhu, M.D.; Phone Number: 86-010-59975442; Email: zbtcm@163.com

Participation Criteria

Eligibility Criteria

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

Description

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

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
Experimental: the Sivelestat group; 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; Sivelestat, a specific inhibitor of neutrophil elastase; sodium N-[2-[4-(2,2-dimethylpropionyloxy) phenyl-sulfonylaminobenzoyl]amino-acetate tetrahydrate]; 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; 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; Excipients used for the sivelestat sodium; 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?

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

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Investigators: Principal Investigator: Guangzhi Shi, M.D., Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University; Principal Investigator: Zhigang Zhao, M.D., Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University

Study record dates

Study Major Dates

• Study Start (Anticipated): January 31, 2023
• Primary Completion (Anticipated): January 3, 2024
• Study Completion (Anticipated): January 31, 2024

Study Registration Dates

• First Submitted: January 16, 2023
• First Submitted That Met QC Criteria: January 22, 2023
• First Posted (Estimate): January 24, 2023

Study Record Updates

• Last Update Posted (Estimate): January 24, 2023
• Last Update Submitted That Met QC Criteria: January 22, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; ARDS; Randomized Trial; Sivelestat
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Respiratory Insufficiency; Respiratory Tract Infections; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Sivelestat
• Other Study ID Numbers: HX-B-2022083

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