A Phase Ib Randomized, Placebo-controlled, Double-blinded Study Evaluating the Safety of Ataciguat (HMR1766) in Patients With Moderate Calcific Aortic Valve Stenosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Number of patients experiencing orthostatic hypotension
研究概览
简要总结
This study will determine whether Ataciguat (HMR1766) is well-tolerated in patients with mild to moderate calcific aortic valve stenosis. The primary focus of these studies will be on changes in blood pressure and orthostatic tolerance (i.e., ability to stand up without passing out), and determining whether treatment with Ataciguat results in significant reductions in blood pressure in this patient population.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 50 years
- •Male or female sex
- •Aortic valve area greater than 1.0 cm2 but less than 2.0 cm2
- •Aortic valve calcium levels greater than 300 arbitrary units from chest CT
- •Ejection fraction >50%
排除标准
- •History of orthostatic intolerance or symptomatic hypotension
- •Positive pregnancy test during screening visit
- •Nitrate use or α-antagonist medication use within 24 hours
- •Systolic blood pressure <110 mm Hg
- •Mean systemic arterial pressure <75 mm Hg
- •Severe mitral or aortic regurgitation
- •Retinal or optic nerve problems
- •Recent (≤30 days) acute coronary syndrome
- •Oxygen saturation <90% on room air
- •Congenital valve disease
- •Hepatic dysfunction/elevated liver enzymes
- •Prescription of drugs known to alter nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate signaling (sildenafil, nitrates, etc.)
- •History of orthostatic intolerance
- •Concomitant participation in other trials at Mayo Clinic or elsewhere.
研究组 & 干预措施
Placebo
Placebo gel capsule, dosage matches number of Ataciguat capsules for each respective dose, capsules taken once daily with breakfast for 14 consecutive days.
干预措施: Placebo (Drug)
Ataciguat
Ataciguat, orally administered gel capsule, 50, 100, or 200 mg, once per day with breakfast for 14 consecutive days
干预措施: Ataciguat (Drug)
结局指标
主要结局
Number of patients experiencing orthostatic hypotension
时间窗: Baseline - 14 days
The primary objective of the current study is to determine whether Ataciguat (HMR1766) is well-tolerated by patients with moderate calcific aortic valve stenosis. In this particular patient population, incidence of orthostatic intolerance/symptomatic hypotension is a potential concern.
The change in blood pressure following the transition from sitting to standing
时间窗: Baseline - 14 days
The primary objective of the current study is to determine whether Ataciguat (HMR1766) is well-tolerated by patients with moderate calcific aortic valve stenosis. In this particular patient population, incidence of orthostatic intolerance/symptomatic hypotension is a potential concern. Transitioning from sitting to standing is a functional test that will allow us to examine the effects of Ataciguat on blood pressure regulation in response to a relevant orthostatic stress.
The change in blood pressure following progressive head-up tilt
时间窗: Baseline - 14 days
The primary objective of the current study is to determine whether Ataciguat (HMR1766) is well-tolerated by patients with moderate calcific aortic valve stenosis. In this particular patient population, incidence of orthostatic intolerance/symptomatic hypotension is a potential concern. Tilt table testing will allow us to examine the effects of Ataciguat on blood pressure regulation in response to a tightly controlled orthostatic stress.
Subject self-reports of light-headedness/orthostatic intolerance during the standing test and the head-up tilt testing
时间窗: Baseline - 14 days
The primary objective of the current study is to determine whether Ataciguat (HMR1766) is well-tolerated by patients with moderate calcific aortic valve stenosis. In this particular patient population, incidence of orthostatic intolerance/symptomatic hypotension is a potential concern. Evaluating subject perceptions of light-headedness/orthostatic intolerance will help us to understand the relationship between changes in blood pressure and changes in symptoms in this patient population before and after treatment with Ataciguat.
次要结局
未报告次要终点
研究者
Jordan D. Miller, Ph.D.
Assistant Professor of Surgery
Mayo Clinic