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

Nanjing University

Status and phase: Completed; Phase 3

Conditions: Cardiac Disease

Treatments: Drug: Sivelestat; Other: placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT06276569

2023-LCYJ-MS-26

Details and patient eligibility

About

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.

Full 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.

Enrollment: 382 patients

Sex: All

Ages: 50 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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382 participants in 2 patient groups, including a placebo group

sivelestat group

Experimental group

Description:

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.

Treatment:

Drug: Sivelestat

placebo comparator

Placebo Comparator group

Description:

received an equivalent volume (50ml) of saline continuously administered intravenously at a rate of 0.2 mg/kg/hour.

Treatment:

Other: placebo