Cardiac and Metabolic Effects of Dapagliflozin in the Failing Fontan Circulation: A Phase II, Prospective, Double-Blind Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Mayo Clinic
- 入组人数
- 27
- 试验地点
- 2
- 主要终点
- Pulmonary capillary wedge pressure (PCWP) at rest
研究概览
简要总结
The purpose of this research is to determine whether treatment with the study drug dapagliflozin for 3 months affects peripheral venous pressure at rest and during exercise in adults with failing Fontan circulation.
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)
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
- •Signed informed consent prior to any study specific procedures
- •History of Fontan procedure
- •Male or female subject
- •Symptoms of dyspnea (NYHA II-IV) with no non-cardiac or ischemia explanation
- •Elevated peripheral venous pressure (PVP) at rest or during exercise (≥20 mmHg) ascertained at Visit
- •Patients that have consented to study procedures but do not meet this invasive criterion will be considered as screen failures and will not be randomized.
排除标准
- •Type I diabetes
- •Any of the following medications: Insulin or Pramlintide, Sandostatin, Akeega (abiraterone acetate), Growth Hormone (Somatogrogon-GHLA), Lithium, Chloroquine, Hydroxychloroquine, Thioctic acid (alpha lipoic acid), Empagliflozin or Canagliflozin
- •Recent hospitalization (<30 days) or revascularization (<90 days)
- •Significant valvular heart disease (≥moderate stenosis, >moderate regurgitation)
- •Significant Fontan obstruction with resting SVC-IVC gradient >4 mmHg
- •Primary cardiomyopathy (such as amyloid)
- •Dyspnea due to primary lung disease or myocardial ischemia in the opinion of the investigator
- •Severe anemia (hemoglobin <9 gm/dl)
- •Severe kidney disease (estimated GFR<30) or liver disease
- •Women of childbearing potential not willing to use a medically accepted method of contraception OR who are currently pregnant (confirmed with positive pregnancy test) or breast feeding.
- •History of serious hypersensitivity reaction to dapagliflozin
- •Subjects on dialysis
- •Subjects with severe liver disease with history of decompensation including ascites or encephalopathy or variceal bleeding
- •Single ventricle heart disease without Fontan palliation
- •Those with a history of Fontan takedown
研究组 & 干预措施
Dapagliflozin
干预措施: Dapagliflozin tablet (Drug)
Placebo
干预措施: Placebo Tablet (Drug)
结局指标
主要结局
Pulmonary capillary wedge pressure (PCWP) at rest
时间窗: Baseline, 24 Months
Pulmonary Capillary Wedge pressure will be determined by right heart catheterization with expired gas analysis. Right heart catheterization with expired gas analysis will be performed at rest. Pulmonary Capillary Wedge Pressure is measured in millimeters of mercury (mmHg).
Pulmonary capillary wedge pressure with feet elevated
时间窗: Baseline, 24 Months
Pulmonary Capillary Wedge pressure will be determined by right heart catheterization with expired gas analysis. Right heart catheterization with expired gas analysis will be performed with feet elevated. Pulmonary Capillary Wedge Pressure is measured in millimeters of mercury (mmHg).
Pulmonary capillary wedge pressure at 20W exercise
时间窗: Baseline, 24 Months
Pulmonary Capillary Wedge pressure will be determined by right heart catheterization with expired gas analysis. Right heart catheterization with expired gas analysis will be performed at 20W exercise. Pulmonary Capillary Wedge Pressure is measured in millimeters of mercury (mmHg).
Peripheral venous pressure (PVP) at rest
时间窗: Baseline, 12 Weeks
Peripheral venous pressure (PVP) at rest will be determined by Stress Echocardiogram. Peripheral venous pressure (PVP) is measured in millimeters of mercury (mmHg).
Peripheral venous pressure (PVP) with feet elevated
时间窗: Baseline, 12 Weeks
Peripheral venous pressure (PVP) with feet elevated will be determined by Stress Echocardiogram. Peripheral venous pressure (PVP) is measured in millimeters of mercury (mmHg).
Peripheral venous pressure (PVP) at 20W exercise
时间窗: Baseline, 12 Weeks
Peripheral venous pressure (PVP) at 20W exercise will be determined by Stress Echocardiogram. Peripheral venous pressure (PVP) is measured in millimeters of mercury (mmHg).
次要结局
- Right atrial pressure at rest(Baseline, 24 Months)
- Right atrial pressure with exercise(Baseline, 24 Months)
- Pulmonary artery pressures at rest(Baseline, 24 Months)
- Pulmonary artery pressures with exercise(Baseline, 24 Months)
- Cardiac output at rest(Baseline, 24 Months)
- Cardiac output with exercise(Baseline, 24 Months)
- Peak oxygen consumption (VO2) during exercise(Baseline, 24 Months)
- Change in plasma volume(Baseline, 24 Months)
- Change in blood volume(Baseline, 24 Months)
- SF-36 quality of life (QOL)(Baseline, 24 Months)
- Change in fat mass(Baseline, 24 Months)
- Change in fat free mass(Baseline, 24 Months)
- Peak oxygen consumption (VO2) during exercise(Baseline, 12 Weeks)
- Cardiac output at rest(Baseline, 12 Weeks)
- Cardiac output with exercise(Baseline, 12 Weeks)
- Change in plasma volume(Baseline, 12 Weeks)
- Change in blood volume(Baseline, 12 Weeks)
- SF-36 quality of life (QOL)(Baseline, 12 Weeks)
- Change in fat mass(Baseline, 12 Weeks)
- Change in fat free mass(Baseline, 12 Weeks)
研究者
Luke J. Burchill
Principal Investigator
Mayo Clinic