SGC Stimulation, Perioperative Vascular Reactivity, and Organ Injury in Cardiac Surgery

NCT ID: NCT05812755

Last Updated: 2025-07-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 170 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-19
• Study Completion Date: 2027-11-30

Brief Summary

The goal of this mechanistic clinical trial is to learn about the effects of medications called soluble guanylyl cyclase stimulators on vascular function and markers of kidney and brain injury in patients having heart surgery. The main questions it aims to answer are:

1. Does soluble guanylyl cyclase stimulation improve blood vessel function compared to placebo?

2. Does soluble guanylyl cyclase stimulation decrease markers of kidney injury and brain injury compared to placebo?

Participants will be randomized to a soluble guanylyl cyclase stimulator called vericiguat or placebo, and researchers will compare vascular function and markers of brain and kidney injury to see if vericiguat improves vascular function and reduces markers of injury.

This will provide important information to determine the underlying reasons that patients have some kidney and brain function problems after having heart surgery.

Detailed Description

Patients undergoing elective cardiac surgery will be randomized to the soluble guanylyl cyclase stimulator vericiguat versus placebo before surgery through the day of surgery and vascular function will be quantified using ultrasound and direct assessment of arterial relaxation ex-vivo. Markers of brain and kidney injury will be measured in plasma and urine.

Conditions

Endothelial Dysfunction; Vascular Diseases; Kidney Injury; Brain Disease; Vascular Inflammation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Vericiguat

10 mg vericiguat administered orally once daily for three days (through day of surgery)

Group Type: ACTIVE_COMPARATOR

Vericiguat

Intervention Type: DRUG

Vericiguat 10 mg administered orally starting 2 days prior to heart surgery through the day of surgery

Placebo

placebo administered orally once daily for three days (through day of surgery)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matched placebo administered orally starting 2 days prior to heart surgery through the day of surgery

Interventions

Vericiguat

Vericiguat 10 mg administered orally starting 2 days prior to heart surgery through the day of surgery

Intervention Type: DRUG

Placebo

Matched placebo administered orally starting 2 days prior to heart surgery through the day of surgery

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age ≥18 years

2. Elective open-heart surgery, defined as surgery on the heart or aorta that requires sternotomy or thoracotomy

Exclusion Criteria

1. Intolerance to vericiguat

2. Use of other soluble guanylyl cyclase stimulators or current use of phosphodiesterase-5 inhibitors

3. Pregnancy or breast feeding. Pregnancy will be excluded in women of child-bearing potential by a urine or serum beta hcg test

4. Renal replacement therapy within 30 days prior to screening

5. Estimated glomerular filtration rate <15 ml/min per 1.73 m2 per Chronic Kidney Disease Epidemiology collaboration (CKD-EPI) equation at time of screening

6. Systolic blood pressure less than 120 mmHg at the time of screening

7. Prior kidney transplantation

8. History of significant liver dysfunction (defined as Child-Pugh class C)

9. Surgery scheduled to be performed with circulatory arrest

10. Surgery scheduled to correct a major congenital heart defect

11. Extracorporeal membrane oxygenation (ECMO) prior to surgery

12. Active systemic infection or surgery for infectious endocarditis

13. Ventricular assist device or intraaortic balloon pump support prior to surgery

14. Prisoners

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Marcos G. Lopez

Associate Professor of Anesthesiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marcos Lopez, MD

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University Medical Center

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status: RECRUITING

Countries

United States

Facility Contacts

Marcos G Lopez, MD

Role: primary

marcos.g.lopez@vumc.org

615-936-5894

Other Identifiers

R01HL164909

Identifier Type: NIH

Identifier Source: secondary_id

View Link

222089

Identifier Type: -

Identifier Source: org_study_id