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NCT Number: NCT05812755

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

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.

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Key information

Conditions

Endothelial Dysfunction Brain Disease Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Kidney Injury Nervous System Diseases Vascular Diseases Vascular Inflammation

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Vanderbilt University Medical Center

Nashville, Tennessee, 37204, United States

Location status: Recruiting

Location contact

Marcos G Lopez, MD

CONTACT

[email protected]

615-936-5894

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age ≥18 years
  • Elective open-heart surgery, defined as surgery on the heart or aorta that requires sternotomy or thoracotomy

Exclusion criteria

  • Intolerance to vericiguat
  • Use of other soluble guanylyl cyclase stimulators or current use of phosphodiesterase-5 inhibitors
  • Pregnancy or breast feeding. Pregnancy will be excluded in women of child-bearing potential by a urine or serum beta hcg test
  • Renal replacement therapy within 30 days prior to screening
  • Estimated glomerular filtration rate <15 ml/min per 1.73 m2 per Chronic Kidney Disease Epidemiology collaboration (CKD-EPI) equation at time of screening
  • Systolic blood pressure less than 120 mmHg at the time of screening
  • Prior kidney transplantation
  • History of significant liver dysfunction (defined as Child-Pugh class C)
  • Surgery scheduled to be performed with circulatory arrest
  • Surgery scheduled to correct a major congenital heart defect
  • Extracorporeal membrane oxygenation (ECMO) prior to surgery
  • Active systemic infection or surgery for infectious endocarditis
  • Ventricular assist device or intraaortic balloon pump support prior to surgery
  • Prisoners

Treatment and study plan

Vericiguat

Drug

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

Placebo

Drug

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

Primary outcomes

  1. Brachial artery flow-mediated dilation

    Time frame: Day of surgery

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

  2. Ex vivo vascular relaxation

    Time frame: Day of surgery

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

  3. Ubiquitin C-terminal hydrolase L1 (UCHL1) plasma concentration

    Time frame: Enrollment through postoperative day 2

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

  4. Neutrophil gelatinase associated lipocalin (NGAL) urine concentration

    Time frame: Enrollment through postoperative day 2

    NGAL will be measured in urine to quantify effects of vericiguat vs. placebo on markers of renal injury (Aim 2 primary renal outcome)

Secondary outcomes

  1. Phosphorylated vasodilator stimulated phosphoprotein (phospho-VASP)

    Time frame: Enrollment through postoperative day 2

    Soluble guanylyl cyclase stimulation will be further quantified as arterial phospho-VASP/VASP ratio(Aim 1 secondary outcome)

  2. Endothelial barrier breakdown - claudin-5

    Time frame: Enrollment through postoperative day 2

    Endothelial barrier breakdown will be quantified as plasma concentration of claudin-5 (Aim 1 secondary outcome)

  3. Endothelium mediated inflammation and coagulation - plasminogen activator inhibitor-1 (PAI-1)

    Time frame: Enrollment through postoperative day 2

    Endothelium mediated inflammation and coagulation will be quantified as plasma concentration of PAI-1 (Aim 1 secondary outcome)

  4. Endothelial Activation - intercellular adhesion molecule 1 (ICAM1)

    Time frame: Enrollment through postoperative day 2

    Endothelial activation will be quantified as plasma concentrations of ICAM1 (Aim 1 secondary outcome)

Other outcomes

  1. Exploratory clinical outcome: serum creatinine

    Time frame: Postoperative day 0 up to 1 year postoperatively (e.g., approximately 1 year after the day of surgery)

    Serum creatinine

  2. Exploratory clinical outcome: Kidney Disease Improving Global Outcomes (KDIGO) Acute Kidney Injury (AKI)

    Time frame: Postoperative day 0 up to 1 year postoperatively (e.g., approximately 1 year after the day of surgery)

    Incidence of KDIGO creatinine criteria AKI

  3. Exploratory clinical outcome: delirium

    Time frame: Postoperative day 0 to 10 days postoperatively

    Incidence (percent of participants) with a positive delirium exam measured using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).

  4. Exploratory clinical outcome: delirium severity

    Time frame: Postoperative day 0 to 10 days postoperatively

    Severity of delirium measured using the CAM-ICU-7 score for at least 3 days postoperatively up to 10 days postoperatively for participants who remain in ICU. This is a 7 point scale score with higher scores indicating higher severity of delirium

  5. Exploratory clinical outcome: Infection

    Time frame: Postoperative day 0 to 10 days postoperatively

    Infection defined as initiation of antibiotics postoperatively not part of perioperative antibiotic prophylaxis.

  6. Exploratory clinical outcome: Respiratory failure

    Time frame: Postoperative day 0 to hospital discharge (e.g., up to approximately 30 days following surgery)

    Respiratory failure defined as the need for mechanical ventilation

  7. Exploratory clinical outcome: Thrombocytopenia

    Time frame: Postoperative day 0 to hospital discharge(e.g., up to approximately 30 days following surgery)

    Thrombocytopenia defined at platelet count less than 50,000

  8. Exploratory clinical outcome: Arrythmia

    Time frame: Postoperative day 0 to hospital discharge (e.g., up to approximately 30 days following surgery)

    Arrhythmia defined the onset of new atrial or ventricular dysrhythmia

  9. Exploratory clinical outcome: Intensive care unit (ICU) length of stay

    Time frame: Postoperative day 0 to until discharge from the ICU (e.g. up to approximately 10 days following surgery)

    ICU length of stay in days

  10. Exploratory clinical outcome: Hospital length of stay

    Time frame: Postoperative day 0 to hospital discharge (e.g., up to approximately 30 days following surgery)

    Hospital length of stay in days

  11. Exploratory clinical outcome: Death

    Time frame: Postoperative day 0 to one year postoperatively

    Mortality measured up to one year

  12. Exploratory cognitive status outcome: Telephone interview for cognitive status

    Time frame: 6 months postoperatively

    Six-month follow-up (Telephone Interview for Cognitive Status) obtained by phone interview. Maximum score is 41 and lower score indicates worse cognitive function.

  13. Exploratory functional status outcome: Katz Activities of Daily Living (ADL) assessment

    Time frame: 6 months postoperatively

    Activities of daily living will be assessed with the Katz ADL assessment via phone interview. This survey assesses independence in 6 activities, and will be summarized as the average number of independent activities.

  14. Exploratory functional status outcome: Pfeffer functional activities questionnaire

    Time frame: 6 months postoperatively

    Activities of daily living will be assessed with the Pfeffer functional activities questionnaire via phone interview. Maximum score is 30. A score of greater than 9 indicates impaired function and possible cognitive impairment.

Sponsors and collaborators

Lead sponsor

Vanderbilt University Medical Center

Other

Collaborators

  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Official study title

The Effects of Soluble Guanylyl Cyclase Stimulation on Perioperative Vascular Reactivity and Organ Injury in Cardiac Surgery

Acronym: SOLSTICE

Important dates

Study start
2023
Primary completion
2026
Study completion
2027
First posted
Apr 14, 2023
Registry last updated
Jul 8, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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