Efficacy and Safety of Sivelestat in Preventing Postoperative Acute Respiratory Distress Syndrome After Cardiac Surgery :a Single Centre Random Control Trial.

Phase 3

Not yet recruiting

• Conditions: Cardiac Disease
• Interventions: Other: placebo; Drug: Sivelestat

• Registration Number: NCT06276569
• Lead Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Brief Summary

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

Detailed Description

This study is being performed as a randomized, single-blind, placebo-controlled trial conducted in 384 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 drug administration occurring within 6 hours 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 Timeline

• Study First Submitted: 2024-01-31
• Status Verified: 2024-02
• Study Start: 2024-02-18
• Study First Submitted QC: 2024-02-21
• Study First Posted: 2024-02-26
• Last Update Submitted: 2024-02-26
• Last Update Posted: 2024-02-28
• Primary Completion: 2026-06-30
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 384

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo comparator	placebo	received an equivalent volume (50ml) of saline continuously administered intravenously at a rate of 0.2 mg/kg/hour.
experimental	Sivelestat	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.

Primary Outcome Measures

Name	Time	Method
Murray socre	postoperative day 1, 3, 5 and 7	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
Oxygenation index	postoperative day 1, 3, 5 and 7	SpO2 /FIO2
Acute physiology and chronic health evaluation(APACHE II) socre	postoperative day 1, 3, 5 and 7	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
In-hospital time	postoperative 28 days	All time during hospitalization
Inflammatory index	postoperative day 1, 3, 5 and 7	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\[MPO, ng/ml\]
Myocardial injury marker	postoperative day 1, 3, 5 and 7	myoglobin\[Myo, ng/ml\], CK-MB\[ng/ml\], hs-cTnI\[ng/ml\]
ICU time	postoperative 28 days	Time to stay in the intensive care unit
30-day all-cause mortality	postoperative 30 dayS	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
90-day all-cause mortality	postoperative 90 days	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