Hemodynamic Effects of a Novel Myeloperoxidase Inhibitor With Exercise in Heart Failure With Preserved Ejection Fraction - A Randomized, Double-Blind, Placebo Controlled Proof of Principle Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in Exercise Pulmonary Capillary Wedge Pressure (PCWP)
研究概览
简要总结
Researchers are studying the effect of a single dose of oral myeloperoxidase on heart failure versus placebo.
详细描述
Enroll subjects with a normal ejection fraction referred to the catheterization laboratory for evaluation of breathlessness or shortness of breath. Perform safety lab sampling, echocardiography, arterial tonometry for pulse wave analysis, and assessment of endothelial function prior to administration of study drug. During the catheterization researchers will perform blood draws, assess baseline exercise capacity at rest and during exercise. Researchers will also do an echocardiogram to take measurements of the heart. Subjects will be randomized to one of two groups, Oral Myeloperoxidase Inhibitor or placebo group. Study drug or placebo will be administered followed by a repeat of the baseline catheterization assessments. At the conclusion of the second exercise test the subject will be moved to a room and monitored overnight for safety. Repeat blood draws, echocardiogram, endothelial function test, and heart monitoring will be completed. The subject will be asked to follow up with the researchers between 9-14 days after the study drug dosage. The subjects history and blood work will be completed at that visit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Only research pharmacy staff will be aware of randomization scheme and all study personnel and subjects will remain blinded.
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females of non-childbearing potential
- •Age ≥ 30 years
- •Symptoms of dyspnea (II-IV) at the time of screening
- •Ejection Fraction (EF) ≥ 50% as determined on imaging study within 12 months of enrollment
- •Catheterization documented elevated filling pressures at rest (PCWP ≥15) or with exercise (PCWP ≥25)
排除标准
- •Use of nitrates, phosphodiesterase 5 inhibitors or other NO-providing therapy in the past 24 hours of screening
- •Significant valvular disease (>moderate left-sided regurgitation, >mild stenosis)
- •Requirement of intravenous heparin at the start of case
- •Severe pulmonary parenchymal disease
- •Acute coronary syndrome or coronary disease requiring revascularization in the judgement of investigators
- •Resting systolic blood pressure < 100 mmHg
- •Constrictive pericarditis
- •Infiltrative, restrictive, or hypertrophic obstructive cardiomyopathies
- •Previous anaphylaxis to any drug
- •Pregnancy or breastfeeding mothers
- •High Output heart failure
- •Active thyroid disease
- •Treatment with a new chemical entity (defined as a compound which has not been approved for marketing) within the preceding 3 months
- •Patients with any prior allergy to propylthiouracil
研究组 & 干预措施
AZD4831 Oral myeloperoxidase inhibitor
Patient may take 30 mg of oral myeloperoxidase inhibitor following baseline right heart catheterization.
干预措施: AZD4831 Oral Myeloperoxidase Inhibitor (Drug)
Placebo
Patient may take 30 mg of placebo oral capsule following baseline right heart catheterization.
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
Change in Exercise Pulmonary Capillary Wedge Pressure (PCWP)
时间窗: Baseline, approximately 30 minutes after study drug administration
Pulmonary capillary wedge pressure (PCWP) provides an indirect estimate of left atrial pressure (LAP). PCWP is the pressure measured by wedging a pulmonary catheter with an inflated balloon into a small pulmonary arterial branch. The exercise PCWP values are obtained at 20 Watt workload, measured in mmHg.
Exercise Pulmonary Capillary Wedge Pressure (PCWP)
时间窗: Baseline
Pulmonary capillary wedge pressure (PCWP) provides an indirect estimate of left atrial pressure (LAP). PCWP is the pressure measured by wedging a pulmonary catheter with an inflated balloon into a small pulmonary arterial branch. The exercise PCWP values are obtained at 20 Watt workload, measured in mmHg.
次要结局
- Change in Resting Pulmonary Capillary Wedge Pressure (PCWP)(Baseline, approximately 30 minutes after study drug administration)
- Change in Exercise Central Pressures(Baseline, approximately 30 minutes after study drug administration)
- Change in Resting Central Pressures(Baseline, approximately 30 minutes after study drug administration)
- Change in Exercise Transmyocardial Lactate Ratio(Baseline, approximately 30 minutes after drug administration)
- Change in Resting Transmyocardial Lactate Ratio(Baseline, approximately 30 minutes after drug administration)
研究者
Barry Borlaug
Principle Investigator
Mayo Clinic