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

Cardiac Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06276569
• Other study ID #: 2023-LCYJ-MS-26
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: February 18, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: February 2024
• Source: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 384
• Est. completion date: December 31, 2026
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lung Injury
• Cardiac Disease
• Heart Diseases
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn

Intervention

Drug:
• Sivelestat
(1)Experimental group: Received intravenous sivelestat sodium within 6 hours of 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.

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Oxygenation index	SpO2 /FIO2	postoperative day 1, 3, 5 and 7
Primary	Inflammatory index	WBC[×109/L], Neutrophil[NEU,%], Interleukin(IL)-1ß[pg/mL], IL-6[pg/mL], IL-8[pg/mL], TNF-a[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
Primary	Myocardial injury marker	myoglobin[Myo, ng/ml], CK-MB[ng/ml], hs-cTnI[ng/ml]	postoperative day 1, 3, 5 and 7
Primary	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
Primary	Murray 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
Primary	ICU time	Time to stay in the intensive care unit	postoperative 28 days
Primary	In-hospital time	All time during hospitalization	postoperative 28 days
Primary	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
Primary	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