Cardiopulmonary Bypass, Cardio Vascular Disease
Conditions
Keywords
cardiovascular
Brief summary
The purpose of this study is to evaluate the efficacy and safety of perioperative vericiguat in patients undergoing cardiovascular surgery. Patients at high risk of heart failure or with confirmed cardiac dysfunction will be randomly assigned to receive either vericiguat plus standard of care or standard of care alone. The primary objective is to determine whether perioperative administration of vericiguat can reduce (I) the Incidence of Early Postoperative Hemodynamic Deterioration or Clinically Significant Myocardial Injury; (II) Incidence of Major Sterile Inflammation-Related Organ Injuries (MSIRI), and the incidence of Major Adverse Cardiovascular Events (MACE) within 12 months after surgery.
Detailed description
Perioperative pathophysiological changes in cardiovascular surgery, such as stress response, ischemia-reperfusion injury, and endothelial dysfunction, often lead to an increased risk of postoperative complications, especially postoperative heart failure and ventricular remodeling. This study hypothesizes that vericiguat, a novel oral soluble guanylate cyclase (sGC) stimulator, can improve endothelial function and reduce postoperative cardiovascular complications by repairing the impaired NO-sGC-cGMP signaling pathway. This is a multicenter, randomized, parallel-group, controlled trial. A total of 600 eligible patients will be randomized in a 1:1 ratio. The experimental group will receive oral vericiguat (starting at 2.5 mg once daily 3 days before surgery, and up-titrated to a target dose of 10 mg once daily postoperatively) in addition to standard perioperative care for 6 months. The control group will receive standard perioperative care alone.
Interventions
DRUGVericiguat
Patients will receive oral vericiguat in addition to standardized perioperative care. Vericiguat will be initiated 3 days before surgery at a dose of 2.5 mg once daily. Postoperatively, upon resumption of enteral nutrition, vericiguat will be continued and gradually up-titrated every 2 weeks based on blood pressure tolerability to 5 mg, and then to a target dose of 10 mg once daily, taken with food, for a total duration of 1 months.
Patients will receive standardized perioperative cardiovascular surgery care alone, without vericiguat or placebo. Standard care includes preoperative preparation, postoperative monitoring, anti-infection, antiplatelet/anticoagulation, diuretics, beta-blockers, SGLT2 inhibitors, and other symptomatic treatments for heart failure according to current guidelines.
Sponsors
Nanjing Medical University
Beijing Anzhen Hospital
The Affiliated Hospital of Qingdao University
Changzhou First People's Hospital
The First Affiliated Hospital of Guangzhou Medical University
The First Affiliated Hospital of Bengbu Medical University
West China Hospital
Shanghai East Hospital, China
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Aged 18 to 80 years, any sex; * Scheduled to undergo cardiovascular surgery at the study centers, including coronary artery bypass grafting (CABG), heart valve replacement/repair, and great vessel surgery; * Preoperative evaluation indicates a high risk of heart failure or confirmed cardiac dysfunction; * Systolic blood pressure (SBP) \>= 100 mmHg; * Expected to complete the 6-month postoperative follow-up; * Signed written informed consent by the patient or their authorized representative.
Exclusion criteria
* Current use of other sGC stimulators or phosphodiesterase type 5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil); * Severe hypotension (symptomatic hypotension or resting SBP \< 90 mmHg); * Severe hepatic or renal dysfunction (Hepatic: Child-Pugh class C, or ALT/AST \> 3 times the upper limit of normal; Renal: eGFR \< 15 mL/min/1.73m\^2, or requiring chronic dialysis); * Malignant tumors, severe hematological diseases, or severe malnutrition (albumin \< 25 g/L); * Known allergy to vericiguat or placebo components; * Pregnant or lactating women, or those planning to become pregnant during the study period; * Currently participating in other interventional clinical trials; * Moderate to severe cognitive impairment without a fixed guardian, unable to cooperate with treatment and follow-up; * Confirmed severe infection, sepsis, or septic shock preoperatively.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Early Postoperative Hemodynamic Deterioration or Clinically Significant Myocardial Injury | Up to 7 days postoperatively (or until ICU discharge, whichever comes first). | A composite endpoint defined as the occurrence of any of the following within 7 days after surgery: 1. Severe Hemodynamic Deterioration (Low Cardiac Output Syndrome, LCOS): Defined by the need for new mechanical circulatory support (e.g., IABP, ECMO) postoperatively, OR a Vasoactive-Inotropic Score (VIS) $\\ge$ 15 sustained for at least 12 consecutive hours. 2. Clinically Significant Perioperative Myocardial Infarction/Injury: Based on the Fourth Universal Definition of Myocardial Infarction (Type 5) or ARC-2 criteria, defined as severe elevation of cardiac biomarkers (e.g., cTn \> 10x 99th percentile URL) accompanied by new ischemic ECG changes or new regional wall motion abnormalities on echocardiography. 3. Cardiovascular Death within 7 days. |
| Incidence of Major Adverse Cardiovascular Events (MACE) | Up to 6 months postoperatively | MACE is defined as a composite endpoint including: cardiovascular death, non-fatal myocardial infarction, ischemic stroke, severe arrhythmia, and readmission due to worsening heart failure. |
| Incidence of Major Sterile Inflammation-Related Organ Injuries (MSIRI) | Up to 7 days postoperatively. | A composite clinical endpoint defined as the occurrence of any of the following severe sterile inflammatory complications within 7 days after surgery, in the absence of proven bacterial infection (defined as negative blood/sputum cultures AND Procalcitonin \[PCT\] \< 0.5$ ng/mL): |
| Maximum Sequential Organ Failure Assessment (SOFA) Score | Up to 7 days postoperatively. | The SOFA score evaluates 6 organ systems (respiratory, coagulation, liver, cardiovascular, central nervous system, and renal), with each system scored from 0 (normal) to 4 (highest degree of dysfunction). The total score ranges from 0 to 24, where higher scores indicate more severe multi-organ dysfunction. The maximum total SOFA score recorded during the first 7 postoperative days will be compared between groups. |
Countries
China
Contacts
CONTACTHong Liu
CONTACTZhi Li, MD
PRINCIPAL_INVESTIGATORSi-chong Qian, MD
Beijing Anzhen Hospital
Outcome results
None listed