SGC Stimulation, Perioperative Vascular Reactivity, and Organ Injury in Cardiac Surgery
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorVanderbilt University Medical Center
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥18 years
Elective open-heart surgery, defined as surgery on the heart or aorta that requires sternotomy or thoracotomy
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Vericiguat
DrugVericiguat 10 mg administered orally starting 2 days prior to heart surgery through the day of surgery
Placebo
DrugMatched placebo administered orally starting 2 days prior to heart surgery through the day of surgery
Treatment groups
170 Participants
are divided into 2 treatment groupsGroup A: VericiguatActive comparator 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
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 surgery2
Ex vivo vascular relaxation
Ex vivo arterial relaxation (percent) in participants with available vascular tissue (Aim 1 primary outcome)
Time frame
Day of surgery3
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)
Time frame
Enrollment through postoperative day 24
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)
Time frame
Enrollment through postoperative day 2Secondary outcomes
1
Phosphorylated vasodilator stimulated phosphoprotein (phospho-VASP)
Soluble guanylyl cyclase stimulation will be further quantified as arterial phospho-VASP/VASP ratio(Aim 1 secondary outcome)
Time frame
Enrollment through postoperative day 22
Endothelial barrier breakdown - claudin-5
Endothelial barrier breakdown will be quantified as plasma concentration of claudin-5 (Aim 1 secondary outcome)
Time frame
Enrollment through postoperative day 23
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)
Time frame
Enrollment through postoperative day 24
Endothelial Activation - intercellular adhesion molecule 1 (ICAM1)
Endothelial activation will be quantified as plasma concentrations of ICAM1 (Aim 1 secondary outcome)
Time frame
Enrollment through postoperative day 2Other outcomes
1
Exploratory clinical outcome: serum creatinine
Serum creatinine
Time frame
Postoperative day 0 up to 1 year postoperatively (e.g., approximately 1 year after the day of surgery)2
Exploratory clinical outcome: Kidney Disease Improving Global Outcomes (KDIGO) Acute Kidney Injury (AKI)
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)3
Exploratory clinical outcome: delirium
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 postoperatively4
Exploratory clinical outcome: delirium severity
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 postoperativelySponsors and contacts
Click on the lead sponsor to view all of their trials.
Vanderbilt University Medical Center
Lead sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator
Source ClinicalTrials.gov