Efficacy and Safety of Sivelestat in Preventing Postoperative Acute Lung Injury or Acute Respiratory Distress Syndrome After Cardiac Surgery

A Single-center, Randomized, Controlled, Study Evaluating the Efficacy and Safety of Sivelestat Sodium in Preventing Postoperative Acute Lung Injury or Acute Respiratory Distress Syndrome Following Cardiac Surgery

The aim of this study is to assess the effectiveness and safety of sivelestat sodium in preventing acute lung injury and/or acute respiratory distress syndrome (ALI/ARDS) following cardiac surgery, with the objective of providing evidence-based support for its clinical application.

Study Overview

• Status: Completed
• Conditions: Cardiac Disease
• Intervention / Treatment: Other: placebo; Drug: Sivelestat

Detailed Description

This study is being performed as a randomized, placebo-controlled trial conducted in 442 patients who met the inclusion and exclusion criteria and were scheduled for elective cardiac surgery. Following informed consent, patients were randomly assigned to either the experimental group or the control group, with the study drug administered after transfer to the ICU post-surgery. In the experimental group, sivelestat was dissolved in 0.9% sodium chloride injection and diluted with 50ml of the same solution to achieve a dose of 4.8mg/kg/day; this mixture was then placed in a sealed package and administered intravenously at a rate of 0.2 mg/kg/h for seven consecutive days. The control group received an equivalent volume (50ml) of saline continuously administered intravenously at a rate of 0.2 mg/kg/hour. Demographic and clinical information, including admission diagnosis, underlying diseases, medical history, surgical history, details of the surgical procedure, postoperative complications, and in-hospital outcomes were collected from all participants. The primary outcome is the incidence of postoperative ARDS. Secondary outcome measures include data collection on the following parameters: elevated inflammatory response indices (WBC>20×109/L; IL-6>301.88mg/ml; CRP>49.76mg/L; PCT>2.18ng/ml) on postoperative days 1, 3, 5, and 7; APACHE II score; Murray lung injury score; incidence of severe pneumonia; mechanical ventilation-free rate at day 28; mortality rates at both day 28 and day 90. Adverse events such as liver injury, leukopenia, and thrombocytopenia resulting from sivelestat treatment were also monitored. Additionally,during the follow-up period, mortality within a 90-day period will be recorded.

• Study Type: Interventional
• Enrollment (Actual): 382
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Nanjing, China
    • The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients aged between 50 and 80 years old.
2. Both sexes.
3. Patients undergoing elective cardiac surgery;informed consent.

Exclusion Criteria:

1. Patients undergoing emergency surgery.
2. Patients undergoing deep hypothermic circulatory arrest surgery;.
3. Patients with liver and kidney dysfunction (Child-Pugh class B or C, estimated glomerular filtration rate <35 mL/min/1.73 m2).
4. Patients with abnormal baseline inflammatory markers [interleukin-6 (IL6) >10 pg/mL, procalcitonin (PCT) >0.5 ng/mL, C-reactive protein (CRP) >10 mg/L].
5. Patients diagnosed with inflammatory immune disease, infectious disease, or oncological disease; patients receiving other medications that inhibit neutrophil elastase (e.g., ulinastatin, alpha 1-antiprotease).
6. Patients allergic to or intolerant to sodium sivelestat.
7. Pregnant.
8. Patients with prognostic mortality on the European System for Cardiac Surgery Risk Evaluation II (EuroSCORE II) >3% were randomly assigned to either the treatment group or the control group based on the inclusion and exclusion criteria.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo comparator; received an equivalent volume (50ml) of saline continuously administered intravenously at a rate of 0.2 mg/kg/hour.	Other: placebo; 2)Control group: Receiving the same dose of placebo, 50 ml of saline, were administered intravenously at a rate of 0.2 mg/kg throughout the treatment period without any discernible impact on patient's regular treatment regimen.
Experimental: sivelestat group; sivelestat was dissolved in 0.9% sodium chloride injection and diluted with 50ml of the same solution to achieve a dose of 4.8mg/kg/day; this mixture was then placed in a sealed package and administered intravenously at a rate of 0.2 mg/kg/h for seven consecutive days.	Drug: Sivelestat; (1)Experimental group: Received intravenous sivelestat sodium admission to the ICU. Sivelestat sodium was dissolved in 0.9% sodium chloride injection and a one-day dose (4.8mg/kg) was diluted in 50ml of 0.9% sodium chloride injection, which was then sealed for continuous intravenous administration at a rate of 0.2 mg/kg/h for seven consecutive days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxygenation index	SpO2 /FIO2	postoperative day 1, 3, 5 and 7
Inflammatory index	WBC[×109/L], Neutrophil[NEU,%], Interleukin(IL)-1β[pg/mL], IL-6[pg/mL], IL-8[pg/mL], TNF-α[pg/mL], CRP[mg/L], PCT[ng/mL], neutrophil elastase[NE,ng/mL] and myeloperoxidase[MPO, ng/ml]	postoperative day 1, 3, 5 and 7
Acute physiology and chronic health evaluation(APACHE II) socre	Interpretation of APACHE II : minimum 0 and maximum 71; increasing score is associated with an increasing risk of hospital death. acute physiology score, chronic health status score, and age adjustment score	postoperative day 1, 3, 5 and 7
ICU time	Time to stay in the intensive care unit	postoperative 28 days
In-hospital time	All time during hospitalization	postoperative 28 days
90-day all-cause mortality	Proportion of deaths caused by various reasons within a certain period of time (90 days) compared to the total number of people in a certain group	postoperative 90 days
Myocardial injury marker	myoglobin[Myo, ng/ml], CK-MB[ng/ml], hs-cTnI[ng/ml]	postoperative day 1, 3, 5 and 7
30-day all-cause mortality	Proportion of deaths caused by various reasons within a certain period of time (30 days) compared to the total number of people in a certain group	postoperative 30 dayS
Murray socre	Interpretation of Murray socre : the Murray Lung Injury Score, a clinical assessment tool for evaluating the severity of acute lung injury. The score ranges from 0 to 4, with higher scores indicating worse pulmonary function and more severe lung injury.	postoperative day 1, 3, 5 and 7

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Investigators: Study Director: Tuo Pan, MD, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2024
• Primary Completion (Actual): April 30, 2025
• Study Completion (Actual): July 30, 2025

Study Registration Dates

• First Submitted: January 31, 2024
• First Submitted That Met QC Criteria: February 21, 2024
• First Posted (Actual): February 26, 2024

Study Record Updates

• Last Update Posted (Actual): August 6, 2025
• Last Update Submitted That Met QC Criteria: August 2, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Wounds and Injuries; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Thoracic Injuries; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Heart Diseases; Lung Injury; Acute Lung Injury; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Serine Proteinase Inhibitors; Sivelestat
• Other Study ID Numbers: 2023-LCYJ-MS-26

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
• product manufactured in and exported from the U.S.: No