Clinical trial NCT05697016: Sivelestat for Acute Respiratory Distress Syndrome Due to COVID-19
Official title: Sivelestat for the Treatment of Adult Patients With Acute Respiratory Distress Syndrome Due to COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Respiratory Infection Virus
Respiratory Failure
Keywords: ARDS
COVID-19
Sivelestat
Randomized Trial
Lead sponsor: Beijing Tiantan Hospital
Sponsor class: OTHER
First posted: 2023-01-25
Enrollment: 238
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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

Primary outcomes:
measure: PaO2/FiO2 ratio
timeFrame: From randomization to day 7
Secondary outcomes:
measure: Ventilator-Free days
timeFrame: From randomization to day 28
measure: In-hospital mortality
timeFrame: Through study completion, a period of 28 days
measure: Length of hospitalization
timeFrame: Through study completion, a period of 28 days
measure: Intensive care unit (ICU) length of stay
timeFrame: Through study completion, a period of 28 days
Other outcomes:
Locations:
Study officials:
affiliation: Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University
name: Guangzhi Shi, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University
name: Zhigang Zhao, M.D.
role: PRINCIPAL_INVESTIGATOR
References: