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

Phase 4RecruitingNCT05812755

Vanderbilt University Medical Center170 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Enrollment

170

Conditions

Endothelial Dysfunction

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Brachial artery flow-mediated dilation

Percent change in brachial artery diameter from baseline to maximum post-forearm ischemia adjusted for shear-rate (Aim 1 primary outcome).

Time frame: Day of surgery

Ex vivo vascular relaxation

Ex vivo arterial relaxation (percent) in participants with available vascular tissue (Aim 1 primary outcome)

Time frame: Day of surgery

Ubiquitin C-terminal hydrolase L1 (UCHL1) plasma concentration

UCHL1 will be measured in plasma to quantify effects of vericiguat vs. placebo on neuronal injury (Aim 2 primary neuronal outcome)