Study of Sivelestat Sodium in OPCABG

Affiliated Hospital of Nantong University

Status and phase: Enrolling; Phase 2

Conditions: Coronary Artery Disease; Coronary Heart Disease; Coronary Arterial Disease (CAD)

Treatments: Drug: Saline (0.9% NaCl); Drug: Sivelestat Sodium injection 2 h after OPCABG for 72 h

Study type: Interventional

Funder types: Other

Identifiers

NCT07118930

2025-K171-01

Details and patient eligibility

About

The goal of this clinical trial is to learn if drug Sivelestat Sodium works to improve the prognosis of off-pump coronary artery bypass grafting (OPCABG) in adults. It will also learn about the safety of drug Sivelestat Sodium. The main questions it aims to answer are:

• Does drug Sivelestat Sodium have a protective effect on myocardial injury after OPCABG?
• Does Sivelestat Sodium exert a protective effect on myocardial inflammatory stress after OPCABG? Researchers will compare drug Sivelestat Sodium to a placebo (a look-alike substance that contains no drug) to see if drug Sivelestat Sodium works to protect myocardium following OPCABG.

Participants will:

• Accept drug Sivelestat Sodium injection or a placebo 2 h after OPCABG for 72 h.
• Undergo a series of blood tests and echocardiography examinations after the OPCABG.

Full description

1.1 Main Objective To evaluate the protective effect of sivelestat sodium on myocardial injury after off-pump coronary artery bypass grafting (OPCABG).

Key observation indicators include: 1) Myocardial injury markers: high-sensitivity cardiac troponin T (hs-cTnT), creatine kinase isoenzyme (CK-MB), NT-proBNP; 2) Cardiac function imaging indicators: global longitudinal strain (GLS) by echocardiography, left ventricular ejection fraction (LVEF).

1.2 Secondary Objective To evaluate the protective effect of sivelestat sodium on myocardial inflammatory stress after OPCABG.

Key observation indicators include: 1) Changes in inflammatory factors (IL-6, CRP, PCT) levels; 2) Observation of clinical outcomes (mechanical ventilation time, ICU stay time, 30-day adverse events, etc.).

2.1 Research Content and Design Prospective, double-blind, randomized, placebo-controlled trial. Prospective design: Standardized data collection from patient enrollment to follow-up completion to avoid recall bias and selection bias in retrospective studies.

Double-blind implementation: Both the subjects, the surgical team, and the outcome assessors are blinded to the group information.

Placebo control: Normal saline for flushing is used as the control to ensure that the basic treatments (anticoagulation, analgesia, etc.) in both groups are completely consistent.

2.2 Research Subjects Patients undergoing elective off-pump coronary artery bypass grafting. 2.3 Research Steps After randomization, the experimental group is administered sivelestat sodium (specification: 0.1 g/vial, Shanghai Huirun Pharmaceutical) at a rate of 0.2 mg/kg/h continuously. Administration starts within 2 hours after surgery and continues for 72 hours. The placebo group is given normal saline for flushing instead of sivelestat sodium. Concomitant medications: Routine anticoagulation and analgesia are allowed, but glucocorticoids or other NE inhibitors are prohibited. The following indicators are measured at preoperative, 2 hours postoperative, 24 hours postoperative, 48 hours postoperative, and 72 hours postoperative: IL-6 (ELISA, R&D Systems), CRP (immunoturbidimetry), CK-MB, cTnI (chemiluminescence); echocardiography is used to assess myocardial motion and cardiac function.

2.4 Evaluation Indicators (Safety, Efficacy Evaluation Criteria, it is recommended to use the latest international or domestic common standards) Efficacy: Primary endpoint (cTnI reduction ≥ 20%); secondary endpoint (IL-6 reduction ≥ 20%).

Safety: Adverse events are recorded using CTCAE 5.0 grading, and their correlation with the study drug is analyzed (see Table in Section 8).

2.5 Data Management and Statistical Analysis Plan, Data Confidentiality Plan An independent data safety monitoring committee (DSMB) is established for data management.

Unblinding conditions: Only independent staff can unblind when serious adverse events (SAEs) require emergency treatment.

Statistical processing software: SPSS 26.0, Graphpad Prism 10. Statistical methods: Intention-to-treat (ITT) analysis, ANCOVA to correct for baseline, measurement data are expressed as mean ± standard deviation, independent sample t-test for comparison between groups, and repeated measures ANOVA for dynamic changes.

3. Subject Recruitment 3.1 Inclusion Criteria Age 18-75 years old, undergoing elective OPCABG (≥2 bypass vessels). LVEF ≥ 35%, no severe liver or kidney function abnormalities (ALT/AST ≤ 3 times the upper limit, eGFR ≥ 60 mL/min).

Signed informed consent form. 3.2 Exclusion Criteria Emergency surgery, combined valve surgery or aortic surgery. Use of immunosuppressants or potent anti-inflammatory drugs within 30 days before surgery.

Active infection, autoimmune disease, or allergy history. Preoperative liver or kidney dysfunction; preoperative severe cardiopulmonary dysfunction.

3.3 Withdrawal and Termination Criteria Withdrawal criteria: Conversion to cardiopulmonary bypass during surgery; postoperative need for IABP, ECMO, or other circulatory support; death or reoperation within 24 hours postoperatively.

Termination criteria: Severe adverse events (SAE, such as anaphylactic shock, liver failure); subject requests withdrawal or is lost to follow-up.

3.4 Duration of Participation for Study Participants (Each Participation Time and Total Time) The total duration of the study is 2 years. Each individual participant's participation period is from 2 hours postoperatively to 72 hours postoperatively, after which the study will be automatically terminated.

3.5 Recruitment Process (Including Recruitment Procedures, Start Time, Methods, Expected Number of Recruits, and Compensation?) Recruitment will commence after study approval, with the first batch expected to start in August 2025.

Recruitment methods include:

In-hospital channels: Posters in the cardiology outpatient department; scrolling display of study introduction on electronic screens (with a QR code linking to detailed information); recommendation by attending physicians during preoperative consultations.

Out-of-hospital channels: Referrals from partner community hospitals; recruitment information pushed on the hospital's official WeChat account (with an online pre-screening questionnaire attached).

Expected number of recruits: 62 cases (31 in the Sivelestat group + 31 in the placebo group); screening ratio: 80 cases expected to be screened, with 20% excluded (emergency surgery, infection, refusal to participate, etc.).

Enrollment: 62 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Undergoing elective OPCABG (≥2 bridged vessels). LVEF≥35%, no severe liver or kidney function abnormalities (ALT/AST≤3 times the upper limit, eGFR≥60 mL/min). Sign the informed consent form.

Exclusion criteria

• Emergency operation, combined valve surgery or aortic surgery. Usage of immunosuppressants or potent anti-inflammatory drugs within 30 days before the operation.
• Active infections, autoimmune diseases, and allergy history.
• Preoperative liver and kidney dysfunction
• Severe cardiopulmonary insufficiency before the operation.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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62 participants in 2 patient groups, including a placebo group

Sivelestat Sodium

Experimental group

Description:

Sivelestat Sodium injection or a placebo 2 h after OPCABG for 72 h

Treatment:

Drug: Sivelestat Sodium injection 2 h after OPCABG for 72 h

Routine therapy

Placebo Comparator group

Description:

Saline instead of Sivelestat

Treatment:

Drug: Saline (0.9% NaCl)