Clinical trial NCT05812755: SGC Stimulation, Perioperative Vascular Reactivity, and Organ Injury in Cardiac Surgery
Official title: The Effects of Soluble Guanylyl Cyclase Stimulation on Perioperative Vascular Reactivity and Organ Injury in Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Endothelial Dysfunction
Vascular Diseases
Kidney Injury
Brain Disease
Vascular Inflammation
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2023-04-14
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Brachial artery flow-mediated dilation
timeFrame: Day of surgery
measure: Ex vivo vascular relaxation
timeFrame: Day of surgery
measure: Ubiquitin C-terminal hydrolase L1 (UCHL1) plasma concentration
timeFrame: Enrollment through postoperative day 2
measure: Neutrophil gelatinase associated lipocalin (NGAL) urine concentration
timeFrame: Enrollment through postoperative day 2
Secondary outcomes:
measure: Phosphorylated vasodilator stimulated phosphoprotein (phospho-VASP)
timeFrame: Enrollment through postoperative day 2
measure: Endothelial barrier breakdown - claudin-5
timeFrame: Enrollment through postoperative day 2
measure: Endothelium mediated inflammation and coagulation - plasminogen activator inhibitor-1 (PAI-1)
timeFrame: Enrollment through postoperative day 2
measure: Endothelial Activation - intercellular adhesion molecule 1 (ICAM1)
timeFrame: Enrollment through postoperative day 2
Other outcomes:
measure: Exploratory clinical outcome: serum creatinine
timeFrame: Postoperative day 0 up to 1 year postoperatively (e.g., approximately 1 year after the day of surgery)
measure: Exploratory clinical outcome: Kidney Disease Improving Global Outcomes (KDIGO) Acute Kidney Injury (AKI)
timeFrame: Postoperative day 0 up to 1 year postoperatively (e.g., approximately 1 year after the day of surgery)
measure: Exploratory clinical outcome: delirium
timeFrame: Postoperative day 0 to 10 days postoperatively
measure: Exploratory clinical outcome: delirium severity
timeFrame: Postoperative day 0 to 10 days postoperatively
measure: Exploratory clinical outcome: Infection
timeFrame: Postoperative day 0 to 10 days postoperatively
measure: Exploratory clinical outcome: Respiratory failure
timeFrame: Postoperative day 0 to hospital discharge (e.g., up to approximately 30 days following surgery)
measure: Exploratory clinical outcome: Thrombocytopenia
timeFrame: Postoperative day 0 to hospital discharge(e.g., up to approximately 30 days following surgery)
measure: Exploratory clinical outcome: Arrythmia
timeFrame: Postoperative day 0 to hospital discharge (e.g., up to approximately 30 days following surgery)
measure: Exploratory clinical outcome: Intensive care unit (ICU) length of stay
timeFrame: Postoperative day 0 to until discharge from the ICU (e.g. up to approximately 10 days following surgery)
measure: Exploratory clinical outcome: Hospital length of stay
timeFrame: Postoperative day 0 to hospital discharge (e.g., up to approximately 30 days following surgery)
measure: Exploratory clinical outcome: Death
timeFrame: Postoperative day 0 to one year postoperatively
measure: Exploratory cognitive status outcome: Telephone interview for cognitive status
timeFrame: 6 months postoperatively
measure: Exploratory functional status outcome: Katz Activities of Daily Living (ADL) assessment
timeFrame: 6 months postoperatively
measure: Exploratory functional status outcome: Pfeffer functional activities questionnaire
timeFrame: 6 months postoperatively
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University Medical Center
name: Marcos Lopez, MD
role: PRINCIPAL_INVESTIGATOR
References: