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

NCT05812755 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: 222089R01HL164909
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 1

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. 1.Does soluble guanylyl cyclase stimulation improve blood vessel function compared to placebo?
2. 2.Does soluble guanylyl cyclase stimulation decrease markers of kidney injury and brain injury compared to placebo?

Conditions

Endothelial Dysfunction; Vascular Diseases; Kidney Injury; Brain Disease; Vascular Inflammation

Outcome Measures

Primary Outcomes (4)

• 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

Secondary Outcomes (4)

• Phosphorylated vasodilator stimulated phosphoprotein (phospho-VASP)

  Enrollment through postoperative day 2

• Endothelial barrier breakdown - claudin-5

  Enrollment through postoperative day 2

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

  Enrollment through postoperative day 2

• Endothelial Activation - intercellular adhesion molecule 1 (ICAM1)

  Enrollment through postoperative day 2

Other Outcomes (14)

• Exploratory clinical outcome: 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)

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

• Exploratory clinical outcome: delirium

  Postoperative day 0 to 10 days postoperatively

Study Arms (2)

Vericiguat

ACTIVE COMPARATOR

10 mg vericiguat administered orally once daily for three days (through day of surgery)

Drug: Vericiguat

Placebo

PLACEBO COMPARATOR

placebo administered orally once daily for three days (through day of surgery)

Drug: Placebo

Interventions

Vericiguat DRUG

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

Vericiguat

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37204, United States

RECRUITING

MeSH Terms

Conditions

Vascular Diseases; Brain Diseases

Interventions

vericiguat

Condition Hierarchy (Ancestors)

Cardiovascular Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Marcos Lopez, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Anesthesiology

Study Record Dates

• First Submitted: March 28, 2023
• First Posted: April 14, 2023
• Study Start: May 19, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): November 1, 2027
• Last Updated: July 8, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)