The Effects of Soluble Guanylyl Cyclase Stimulation on Perioperative Vascular Reactivity and Organ Injury in Cardiac Surgery
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 170
- 试验地点
- 1
- 主要终点
- Neutrophil gelatinase associated lipocalin (NGAL) urine concentration
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Elective open-heart surgery, defined as surgery on the heart or aorta that requires sternotomy or thoracotomy
排除标准
- •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
研究组 & 干预措施
Placebo
placebo administered orally once daily for three days (through day of surgery)
干预措施: Placebo (Drug)
Vericiguat
10 mg vericiguat administered orally once daily for three days (through day of surgery)
干预措施: Vericiguat (Drug)
结局指标
主要结局
Neutrophil gelatinase associated lipocalin (NGAL) urine concentration
时间窗: Enrollment through postoperative day 2
NGAL will be measured in urine to quantify effects of vericiguat vs. placebo on markers of renal injury (Aim 2 primary renal outcome)
Ex vivo vascular relaxation
时间窗: Day of surgery
Ex vivo arterial relaxation (percent) in participants with available vascular tissue (Aim 1 primary outcome)
Ubiquitin C-terminal hydrolase L1 (UCHL1) plasma concentration
时间窗: Enrollment through postoperative day 2
UCHL1 will be measured in plasma to quantify effects of vericiguat vs. placebo on neuronal injury (Aim 2 primary neuronal outcome)
Brachial artery flow-mediated dilation
时间窗: Day of surgery
Percent change in brachial artery diameter from baseline to maximum post-forearm ischemia adjusted for shear-rate (Aim 1 primary outcome).
次要结局
- Endothelial Activation - intercellular adhesion molecule 1 (ICAM1)(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)
- Phosphorylated vasodilator stimulated phosphoprotein (phospho-VASP)(Enrollment through postoperative day 2)
研究者
Marcos G. Lopez
Associate Professor of Anesthesiology
Vanderbilt University Medical Center