Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| R01HL164909 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
Not provided
Not provided
Not provided
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:
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vericiguat | Active Comparator | 10 mg vericiguat administered orally once daily for three days (through day of surgery) |
|
| Placebo | Placebo Comparator | placebo administered orally once daily for three days (through day of surgery) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vericiguat | Drug | Vericiguat 10 mg administered orally starting 2 days prior to heart surgery through the day of surgery |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Day of surgery |
| Ex vivo vascular relaxation | Ex vivo arterial relaxation (percent) in participants with available vascular tissue (Aim 1 primary outcome) | Day of surgery |
| 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) | Enrollment through postoperative day 2 |
| 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) | Enrollment through postoperative day 2 |
| Measure | Description | Time Frame |
|---|---|---|
| Phosphorylated vasodilator stimulated phosphoprotein (phospho-VASP) | Soluble guanylyl cyclase stimulation will be further quantified as arterial phospho-VASP/VASP ratio(Aim 1 secondary outcome) | Enrollment through postoperative day 2 |
| Endothelial barrier breakdown - claudin-5 |
| Measure | Description | Time Frame |
|---|---|---|
| Exploratory clinical outcome: serum creatinine | Serum creatinine | Postoperative day 0 up to 1 year postoperatively (e.g., approximately 1 year after the day of surgery) |
| Exploratory clinical outcome: Kidney Disease Improving Global Outcomes (KDIGO) Acute Kidney Injury (AKI) |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Marcos Lopez, MD | Vanderbilt University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vanderbilt University Medical Center | Recruiting | Nashville | Tennessee | 37204 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D001927 | Brain Diseases |
| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000603960 | vericiguat |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo | Drug | Matched placebo administered orally starting 2 days prior to heart surgery through the day of surgery |
|
Endothelial barrier breakdown will be quantified as plasma concentration of claudin-5 (Aim 1 secondary outcome) |
| Enrollment through postoperative day 2 |
| 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) | Enrollment through postoperative day 2 |
| Endothelial Activation - intercellular adhesion molecule 1 (ICAM1) | Endothelial activation will be quantified as plasma concentrations of ICAM1 (Aim 1 secondary outcome) | Enrollment through postoperative day 2 |
Incidence of KDIGO creatinine criteria AKI |
| Postoperative day 0 up to 1 year postoperatively (e.g., approximately 1 year after the day of surgery) |
| 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). | Postoperative day 0 to 10 days postoperatively |
| 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 | Postoperative day 0 to 10 days postoperatively |
| Exploratory clinical outcome: Infection | Infection defined as initiation of antibiotics postoperatively not part of perioperative antibiotic prophylaxis. | Postoperative day 0 to 10 days postoperatively |
| Exploratory clinical outcome: Respiratory failure | Respiratory failure defined as the need for mechanical ventilation | Postoperative day 0 to hospital discharge (e.g., up to approximately 30 days following surgery) |
| Exploratory clinical outcome: Thrombocytopenia | Thrombocytopenia defined at platelet count less than 50,000 | Postoperative day 0 to hospital discharge(e.g., up to approximately 30 days following surgery) |
| Exploratory clinical outcome: Arrythmia | Arrhythmia defined the onset of new atrial or ventricular dysrhythmia | Postoperative day 0 to hospital discharge (e.g., up to approximately 30 days following surgery) |
| Exploratory clinical outcome: Intensive care unit (ICU) length of stay | ICU length of stay in days | Postoperative day 0 to until discharge from the ICU (e.g. up to approximately 10 days following surgery) |
| Exploratory clinical outcome: Hospital length of stay | Hospital length of stay in days | Postoperative day 0 to hospital discharge (e.g., up to approximately 30 days following surgery) |
| Exploratory clinical outcome: Death | Mortality measured up to one year | Postoperative day 0 to one year postoperatively |
| Exploratory cognitive status outcome: Telephone interview for cognitive status | Six-month follow-up (Telephone Interview for Cognitive Status) obtained by phone interview. Maximum score is 41 and lower score indicates worse cognitive function. | 6 months postoperatively |
| Exploratory functional status outcome: Katz Activities of Daily Living (ADL) assessment | 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. | 6 months postoperatively |
| Exploratory functional status outcome: Pfeffer functional activities questionnaire | 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. | 6 months postoperatively |