Efficacy and Safety of Sivelestat Sodium and Dexamethasone in the Treatment of ARDS (STAR)

Efficacy and Safety of Sivelestat Sodium and Dexamethasone in the Treatment of ARDS: a Pilot Study of a Prospective, Multicenter, Double-blind, Double-mock Randomized Controlled Clinical Study

The goal of this clinical trial is to evaluate the efficacy and safety of Sivelestat sodium and dexamethasone in the treatment of patients with moderate to severe ARDS. The main questions it aims to answer are:

• Is Sivelestat sodium more effective in the treatment of patients with moderate to severe ARDS compared with placebo?
• Is dexamethasone more effective in the treatment of patients with moderate to severe ARDS compared with placebo? Participants will receive Sivelestat sodium, dexamethasone or placebo. Researchers will compare the efficacy and safety of Sivelestat sodium, dexamethasone and placebo.

Study Overview

• Status: Recruiting
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: Sivelestat sodium; Drug: Dexamethasone placebo; Drug: Dexamethasone; Drug: Sivelestat sodium placebo

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yan Chen; Phone Number: +8613538700762; Email: libby0212@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Run Dong, MD; Phone Number: +8613718704355; Email: dongrun5858@foxmail.com
  • Henan
    • Luoyang, Henan, China
      • Not yet recruiting
      • Luoyang Central Hospital
      • Contact: Chunyan Li
  • Shaanxi
    • Yanan, Shaanxi, China
      • Recruiting
      • Yanan University Affiliated Hospital
      • Contact: Zhiyan Hui
  • Sichuan
    • Mianyang, Sichuan, China
      • Not yet recruiting
      • The Third Hospital of Mianyang
      • Contact: Qionglan Dong

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with moderate-to-severe ARDS in the acute exacerbation phase who meet the diagnostic criteria for moderate-to-severe ARDS
• Receiving tracheal intubation for mechanical ventilation within 72 hours after an episode of moderate-to-severe ARDS
• ARDS onset to randomized grouping within 72 hours (starting at the time of onset documented in the medical record)
• Patient volunteers to participate in the study and signs an informed consent form

Exclusion Criteria:

• Pregnancy or breastfeeding
• brain death
• Advanced cancer or other terminal disease
• History of allergy to Sivelestat Sodium and Dexamethasone
• Severe chronic obstructive pulmonary disease
• History of severe cardiovascular disease, such as heart failure, uncontrolled coronary artery disease, cardiomyopathy, uncontrolled cardiac arrhythmia, uncontrolled hypertension, or history of heart or cerebral infarction within the past six months
• Organ transplant or allogeneic stem cell transplant recipients
• Fatal active fungal infections
• neuromuscular disease that affects voluntary breathing
• Genetic or acquired severe immunodeficiencies such as human immunodeficiency virus (HIV) infection, chronic granulomatous disease, severe combined immunodeficiencies
• Patients and/or legal representatives who sign a Do Not Resuscitate (DNR) advance directive, or who abandon treatment
• Participating in other clinical trials

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sivelestat sodium; Sivelestat sodium and dexamethasone placebo	Drug: Sivelestat sodium; Sevilastat sodium 4.8 mg/kg/d IV continuous infusion for 14 days or ICU length of stay (within 14 days); Drug: Dexamethasone placebo; Dexamethasone placebo 10 mg IV once a day for 5 days or until extubation (within 5 days)
Active Comparator: Dexamethasone; Dexamethasone and Sivelestat sodium placebo	Drug: Dexamethasone; Dexamethasone 10 mg IV once a day for 5 days or until extubation (within 5 days); Drug: Sivelestat sodium placebo; Sivelestat sodium placebo 4.8 mg/kg/d IV continuous infusion for 14 days or ICU length of stay (within 14 days)
Placebo Comparator: Placebo; Sivelestat sodium placebo and dexamethasone placebo	Drug: Dexamethasone placebo; Dexamethasone placebo 10 mg IV once a day for 5 days or until extubation (within 5 days); Drug: Sivelestat sodium placebo; Sivelestat sodium placebo 4.8 mg/kg/d IV continuous infusion for 14 days or ICU length of stay (within 14 days)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day ventilator-free days	ventilator-free days within 28 days	28 days after randomization
Informed consent rate	The rate of informed consent	90 days after randomization
Recruitment rate	The rate of recruitment	90 days after randomization
Recruitment compliance rate	The rate of recruitment compliance	90-day after randomization
Protocol adherence rate	The rate of protocol adherence	90 days after randomization
Completion of follow-up visits	The rate of completion of follow-up visits	90 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day mortality	28-day mortality	28 days after randomization
90-day mortality	90-day mortality	90 days after randomization
28-day length of stay	The time interval between randomization and transfer out of ICU. Recorded as 28 days for those who were not transferred out of the ICU 28 days after randomization or those who died during ICU stay	28 days after randomization
28-day organ support free day	Days without intensive care-based respiratory or cardiovascular organ support within 28 days of randomization.	28 days after randomization
Sequential organ failure assessment (SOFA)	Sequential organ failure assessment (SOFA) score evaluation within 14 days. The minimum value is 0 and maximum value is 24, and higher scores mean a worse outcome.	14 days after randomization
Murray's acute lung injury score	Murray's acute lung injury score within 14 days after randomization. The minimum value is 0 and maximum value is 4, and higher scores mean a worse outcome.	14 days after randomization
C-reactive protein (CRP)	C-reactive protein (CRP)	14 days after randomization
Interleukin-6 (IL-6)	Interleukin-6 (IL-6)	14 days after randomization
Interleukin-8 (IL-8)	Interleukin-8 (IL-8)	14 days after randomization
Procalcitonin (PCT)	Procalcitonin (PCT)	14 days after randomization
Neutrophil-to-lymphocyte Ratio (NLR)	Neutrophil-to-lymphocyte Ratio (NLR)	14 days after randomization
Neutrophil elastase	Neutrophil elastase level of blood and alveolar fluid	14 days after randomization
New-onset infection rate	Rate of new-onset infection	28 days after randomization
Re-intubation rate	Rate of unplanned re-intubation	28 days after randomization
Adverse event	Pneumatic trauma (pneumothorax, mediastinal emphysema, subcutaneous emphysema, or imaging findings), infection, sepsis, respiratory acidosis, severe acidosis (pH < 7.10), refractory hypoxemia (PaO2 < 55 mmHg), severe hypotension (mean arterial pressure < 65 mmHg), new-onset arrhythmia (new-onset atrial fibrillation or supraventricular tachycardia), cardiac arrest, and all serious adverse events	28 days after randomization

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Peking University; Shanghai Huilun Pharmaceutical Co., Ltd.
• Investigators: Study Chair: Bin Du, MD, Peking Union Medical College

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: March 10, 2024
• First Submitted That Met QC Criteria: April 26, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Estimated): June 4, 2024
• Last Update Submitted That Met QC Criteria: June 2, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Serine Proteinase Inhibitors; Glycine Agents; Dexamethasone; Dexamethasone acetate; BB 1101; Glycine; Sivelestat
• Other Study ID Numbers: K5321

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD will be shared upon proper requirement.
• IPD Sharing Time Frame: After publication of the study.
• IPD Sharing Access Criteria: Upon proper requirement sent to the primary investigator.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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