Back to resultsSGC Stimulation, Perioperative Vascular Reactivity, and Organ Injury in Cardiac Surgery (SOLSTICE)
Primary Purpose
Endothelial Dysfunction, Vascular Diseases, Kidney Injury
Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Vericiguat
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Endothelial Dysfunction
Eligibility Criteria
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
Sites / Locations
- Vanderbilt University Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Vericiguat
Placebo
Arm Description
10 mg vericiguat administered orally once daily for three days (through day of surgery)
placebo administered orally once daily for three days (through day of surgery)
Outcomes
Primary Outcome Measures
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).
Ex vivo vascular relaxation
Ex vivo arterial relaxation (percent) in participants with available vascular tissue (Aim 1 primary outcome)
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)
Neutrophil gelatinase associated lipocalin (NGAL) urine concentration
NGAL will be measured in urine to quantify effects of vericiguat vs. placebo on markers of renal injury (Aim 2 primary renal outcome)
Secondary Outcome Measures
Phosphorylated vasodilator stimulated phosphoprotein (phospho-VASP)
Soluble guanylyl cyclase stimulation will be further quantified as arterial phospho-VASP/VASP ratio(Aim 1 secondary outcome)
Endothelial barrier breakdown - claudin-5
Endothelial barrier breakdown will be quantified as plasma concentration of claudin-5 (Aim 1 secondary outcome)
Endothelium mediated inflammation and coagulation - plasminogen activator inhibitor-1 (PAI-1)
Endothelium mediated inflammation and coagulation will be quantified as plasma concentration of PAI-1 (Aim 1 secondary outcome)
Endothelial Activation - intercellular adhesion molecule 1 (ICAM1)
Endothelial activation will be quantified as plasma concentrations of ICAM1 (Aim 1 secondary outcome)
Full Information
NCT ID
NCT05812755
First Posted
March 28, 2023
Last Updated
July 5, 2023
Sponsor
Vanderbilt University Medical Center
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT05812755
Brief Title
SGC Stimulation, Perioperative Vascular Reactivity, and Organ Injury in Cardiac Surgery
Acronym
SOLSTICE
Official Title
The Effects of Soluble Guanylyl Cyclase Stimulation on Perioperative Vascular Reactivity and Organ Injury in Cardiac Surgery
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 19, 2023 (Actual)
Primary Completion Date
October 2026 (Anticipated)
Study Completion Date
November 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University Medical Center
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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:
Does soluble guanylyl cyclase stimulation improve blood vessel function compared to placebo?
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Endothelial Dysfunction, Vascular Diseases, Kidney Injury, Brain Disease, Vascular Inflammation
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
170 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Vericiguat
Arm Type
Active Comparator
Arm Description
10 mg vericiguat administered orally once daily for three days (through day of surgery)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
placebo administered orally once daily for three days (through day of surgery)
Intervention Type
Drug
Intervention Name(s)
Vericiguat
Intervention Description
Vericiguat 10 mg administered orally starting 2 days prior to heart surgery through the day of surgery
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matched placebo administered orally starting 2 days prior to heart surgery through the day of surgery
Primary Outcome Measure Information:
Title
Brachial artery flow-mediated dilation
Description
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
Title
Ex vivo vascular relaxation
Description
Ex vivo arterial relaxation (percent) in participants with available vascular tissue (Aim 1 primary outcome)
Time Frame
Day of surgery
Title
Ubiquitin C-terminal hydrolase L1 (UCHL1) plasma concentration
Description
UCHL1 will be measured in plasma to quantify effects of vericiguat vs. placebo on neuronal injury (Aim 2 primary neuronal outcome)
Time Frame
Enrollment through postoperative day 2
Title
Neutrophil gelatinase associated lipocalin (NGAL) urine concentration
Description
NGAL will be measured in urine to quantify effects of vericiguat vs. placebo on markers of renal injury (Aim 2 primary renal outcome)
Time Frame
Enrollment through postoperative day 2
Secondary Outcome Measure Information:
Title
Phosphorylated vasodilator stimulated phosphoprotein (phospho-VASP)
Description
Soluble guanylyl cyclase stimulation will be further quantified as arterial phospho-VASP/VASP ratio(Aim 1 secondary outcome)
Time Frame
Enrollment through postoperative day 2
Title
Endothelial barrier breakdown - claudin-5
Description
Endothelial barrier breakdown will be quantified as plasma concentration of claudin-5 (Aim 1 secondary outcome)
Time Frame
Enrollment through postoperative day 2
Title
Endothelium mediated inflammation and coagulation - plasminogen activator inhibitor-1 (PAI-1)
Description
Endothelium mediated inflammation and coagulation will be quantified as plasma concentration of PAI-1 (Aim 1 secondary outcome)
Time Frame
Enrollment through postoperative day 2
Title
Endothelial Activation - intercellular adhesion molecule 1 (ICAM1)
Description
Endothelial activation will be quantified as plasma concentrations of ICAM1 (Aim 1 secondary outcome)
Time Frame
Enrollment through postoperative day 2
Other Pre-specified Outcome Measures:
Title
Exploratory clinical outcome: serum creatinine
Description
Serum creatinine
Time Frame
Postoperative day 0 up to 1 year postoperatively (e.g., approximately 1 year after the day of surgery)
Title
Exploratory clinical outcome: Kidney Disease Improving Global Outcomes (KDIGO) Acute Kidney Injury (AKI)
Description
Incidence of KDIGO creatinine criteria AKI
Time Frame
Postoperative day 0 up to 1 year postoperatively (e.g., approximately 1 year after the day of surgery)
Title
Exploratory clinical outcome: delirium
Description
Incidence (percent of participants) with a positive delirium exam measured using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).
Time Frame
Postoperative day 0 to 10 days postoperatively
Title
Exploratory clinical outcome: delirium severity
Description
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
Time Frame
Postoperative day 0 to 10 days postoperatively
Title
Exploratory clinical outcome: Infection
Description
Infection defined as initiation of antibiotics postoperatively not part of perioperative antibiotic prophylaxis.
Time Frame
Postoperative day 0 to 10 days postoperatively
Title
Exploratory clinical outcome: Respiratory failure
Description
Respiratory failure defined as the need for mechanical ventilation
Time Frame
Postoperative day 0 to hospital discharge (e.g., up to approximately 30 days following surgery)
Title
Exploratory clinical outcome: Thrombocytopenia
Description
Thrombocytopenia defined at platelet count less than 50,000
Time Frame
Postoperative day 0 to hospital discharge(e.g., up to approximately 30 days following surgery)
Title
Exploratory clinical outcome: Arrythmia
Description
Arrhythmia defined the onset of new atrial or ventricular dysrhythmia
Time Frame
Postoperative day 0 to hospital discharge (e.g., up to approximately 30 days following surgery)
Title
Exploratory clinical outcome: Intensive care unit (ICU) length of stay
Description
ICU length of stay in days
Time Frame
Postoperative day 0 to until discharge from the ICU (e.g. up to approximately 10 days following surgery)
Title
Exploratory clinical outcome: Hospital length of stay
Description
Hospital length of stay in days
Time Frame
Postoperative day 0 to hospital discharge (e.g., up to approximately 30 days following surgery)
Title
Exploratory clinical outcome: Death
Description
Mortality measured up to one year
Time Frame
Postoperative day 0 to one year postoperatively
Title
Exploratory cognitive status outcome: Telephone interview for cognitive status
Description
Six-month follow-up (Telephone Interview for Cognitive Status) obtained by phone interview. Maximum score is 41 and lower score indicates worse cognitive function.
Time Frame
6 months postoperatively
Title
Exploratory functional status outcome: Katz Activities of Daily Living (ADL) assessment
Description
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.
Time Frame
6 months postoperatively
Title
Exploratory functional status outcome: Pfeffer functional activities questionnaire
Description
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.
Time Frame
6 months postoperatively
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marcos Lopez, MD
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37204
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marcos G Lopez, MD
Phone
615-936-5894
Email
marcos.g.lopez@vumc.org
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
SGC Stimulation, Perioperative Vascular Reactivity, and Organ Injury in Cardiac Surgery
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