A Multi-Center, Double-Blind, Randomized, Placebo-controlled, Crossover Study to Assess the Clinical Benefit of Midodrine Hydrochloride in Subjects With Moderate to Severe Neurogenic Orthostatic Hypotension
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 24
- 试验地点
- 11
- 主要终点
- Time to Onset of Near-syncopal Symptoms During Tilt Table Testing
研究概览
简要总结
The purpose of this clinical study is to evaluate the clinical effect of midodrine hydrochloride (ProAmatine®) compared to placebo in patients with orthostatic hypotension by measuring the time to onset of near syncopal symptoms and assessing several cardiovascular measurements, such as heart rate, blood pressure, and ECG, using the tilt table test.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The male or female subjects must be 18 years of age or older and ambulatory. (Subjects must not require assistance with a walker or wheelchair to perform regular daily activities at all times.)
- •Women of childbearing potential must have a negative serum beta HCG pregnancy test at screening and baseline.
- •The subject has been diagnosed with symptomatic orthostatic hypotension due to Parkinson's disease, multiple system atrophy, pure autonomic failure or autonomic neuropathy (i.e. neurogenic orthostatic hypotension).
- •The subject manifests one of the following symptoms while standing or has a history of one of the following when not treated for orthostatic hypotension: dizziness, lightheadedness, feeling faint or feeling like they may black out.
- •The subject is willing and able to undergo the procedures required by this protocol including morning office visits, assessment completion, protocol compliance and participation in the wash-out period.
- •The subject has signed an Institutional-Review-Board approved written informed consent form prior to any study procedures taking place.
排除标准
- •The subject is a pregnant or lactating female.
- •The subject has pre-existing sustained supine hypertension greater than 180 mm Hg systolic and 110 mm Hg diastolic.
- •The subject is taking medications such as vasodilators, pressors, diuretics, ACE inhibitors, angiotensin receptor blockers, beta-blockers, combined alpha and beta-blockers, MAOI's, herbals or specific mixed effect medications.
- •The Principal Investigator deems any laboratory test abnormality clinical significant.
- •The subject has a diagnosis of any of the following disorders at the time of screening: pheochromocytoma; cardiac conditions including: congestive heart failure within the previous 6 months, myocardial infarction within the previous 6 months, symptomatic coronary artery disease, history of ventricular tachycardia, or uncontrolled cardiac arrhythmias; thyrotoxicosis; uncontrolled diabetes mellitus (uncontrolled defined as a HgbA1c greater than or equal to 10%); history of cerebrovascular accident, transient ischemic attack (TIA) or symptomatic carotid artery stenosis within the previous 6 months; history of coagulopathies; pulmonary hypertension; severe psychiatric disorders; renal failure (Creatinine equal to or greater than 2 times the upper limit of normal)
- •The subject has a concurrent chronic or acute illness, disability, or other condition that might confound the results of the tests and/or measurements administered in this trial, or that might increase the risk to the subject.
研究组 & 干预措施
1
干预措施: Midodrine hydrochloride (Drug)
2
干预措施: Placebo (Drug)
结局指标
主要结局
Time to Onset of Near-syncopal Symptoms During Tilt Table Testing
时间窗: 1 hour post-dose
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out.
Time to Onset of Near-syncopal Symptoms During Tilt Table Testing Analysis #2
时间窗: 1 hour post-dose
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near- syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. In this outcome measure, the data analyzed are the same as for Outcome Measure 1 but the summary data are presented as least squares mean (standard error).
Time to Onset of Near-syncopal Symptoms During Tilt Table Testing-Re-analysis With The Koch Procedure
时间窗: 1 hour post-dose
The tilt table test is a 10-minute assessment performed using a manual or automated tilt table in a specialized laboratory. Subjects were moved onto the horizontal table and secured to the table with straps to prevent injury. After an equilibration period of at least 10 minutes with the subject at rest, the test began and the head of the tilt table was elevated to a 70-degree angle over a period of up to 30 seconds. The head-up tilt table test in this study was conducted 1 hour after administration of the study medication. The endpoint was a confirmed report of a near-syncopal symptom(s) (of sufficient severity that caused the patient to ask that the tilt table be returned to the horizontal position). Symptoms of near syncope were defined as dizziness, lightheadedness, feeling faint, or feeling like the subject might black out. The Koch procedure is a 3-step process to analyze results while utilizing the available information on magnitude of differences.
次要结局
- Time to Onset of Near-syncopal Symptoms in The Per-protocol Population Analysis #2(1 hour post-dose)
- Number of Participants With Improvement of Patient CGI-I Scores After Tilt Table Test(1 and 3 hours post-dose)
- Time to Onset of Near-syncopal Symptoms in The Per-protocol Population(1 hour post-dose)
- Final Blood Pressure During Tilt Table Testing(1 hour post-dose)
- Scores for 6 Items of The OHSA(Approximately 1 hour post-dose)
- Heart Rate at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2(1 and 3 hours post-dose)
- Number of Participants With Shifts in Reference to Normal Range For Urinalysis at Discharge(Baseline to discharge)
- Time to Near-syncopal Symptoms at Treatment Visit 1(1 hour post-dose)
- Total Score of the Orthostatic Hypotension Symptom Assessment (OHSA)(Approximately 1 hour post-dose)
- Diastolic Blood Pressure at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2(1 and 3 hours post-dose)
- Duration of The Effect of Treatment at 3 Hours Post-dose(1 and 3 hours post-dose)
- Number of Participants With Improvement of Clinician Clinician's Global Impression- Improvement (CGI-I) Scores After Tilt Table Test(1 and 3 hours post-dose)
- Systolic Blood Pressure at 1 Minute and 10 Minutes Into The Tilt Table Test Conducted 1 and 3 Hours Post-dose at Treatment Visit 2(1 and 3 hours post-dose)
- Number of Participants With Shifts in Reference to Normal Range For Hematology Analytes at Discharge(Baseline to discharge)
- Number of Participants With Shifts in Reference to Normal Range For Clinical Chemistry at Discharge(Baseline to discharge)