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

Vanderbilt University Medical Center

Status and phase: Enrolling; Phase 4

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

Treatments: Drug: Placebo; Drug: Vericiguat

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05812755

R01HL164909 (U.S. NIH Grant/Contract)

222089

Details and patient eligibility

About

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.

Full 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.

Enrollment: 170 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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170 participants in 2 patient groups, including a placebo group

Vericiguat

Active Comparator group

Description:

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

Treatment:

Drug: Vericiguat

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo