A Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Crossover Study to Assess the Clinical Benefit of Midodrine Hydrochloride in Patients With Neurogenic Orthostatic Hypotension
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 140
- 试验地点
- 26
- 主要终点
- Post-treatment Score For Item 1 of The Orthostatic Hypotension Symptom Assessment (OHSA) Scale
研究概览
简要总结
We are seeking male and female patients to voluntarily take part in a clinical research study. Patients must be aged 18 or older and diagnosed with symptomatic orthostatic hypotension (low blood pressure while in the upright position) due to Parkinson's disease, multiple system atrophy, pure autonomic failure or autonomic neuropathies (i.e. neurogenic orthostatic hypotension). Symptoms of low blood pressure include dizziness, lightheadedness, changes in vision and generalized weakness upon standing. The main effect of the drug being studied is to increase blood pressure in the upright position so symptoms will decrease.
The purpose of this clinical study is to further assess the clinical benefit of midodrine hydrochloride (ProAmatine®), an approved treatment for orthostatic hypotension. During the course of the study, participants will receive either ProAmatine® or a placebo. Assessments will be made using questionnaires that measure symptom and activity levels. Blood pressure in the lying down and standing positions will be measured at each visit.
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
- Double
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
- •The male or female patient must be 18 years of age or older and ambulatory.
- •Female patients must be: without menses for at least 12 months prior to screening; surgically sterilized (bilateral tubal ligation or hysterectomy); or practicing adequate means of birth control. Adequate means of birth control is defined as the use of prescribed birth control pills, IUD, or hormonal injections from at least one month prior to screening. Double-barrier methods and abstinence are also acceptable forms of birth control.
- •The patient has been diagnosed with symptomatic orthostatic hypotension due to Parkinson's disease, multiple system atrophy, pure autonomic failure or autonomic neuropathies (i.e. neurogenic orthostatic hypotension).
- •The patient manifests at least 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 patient 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 patient signs an Institutional-Review-Board approved written Informed Consent form prior to any study procedures taking place.
排除标准
- •The patient is pregnant or lactating female.
- •The patient has pre-existing sustained supine hypertension greater than 180 systolic and 110 diastolic mmHg.
- •The patient 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 clinically significant.
- •The patient 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 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 patient 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 patient.
结局指标
主要结局
Post-treatment Score For Item 1 of The Orthostatic Hypotension Symptom Assessment (OHSA) Scale
时间窗: End of 2-week treatment period
Item 1 of the OHSA asked the patient to rate, using a 0-10 scale (0 meaning not bothered and 10 meaning the worst), his or her impression of the severity of dizziness, lightheadedness, feeling faint, or feeling like you might black out whenever he or she was standing and that improved when he or she sat or laid down. Higher scores indicate more severe disease.
Post-treatment OHSA Item 1 Score of United States (US) Participants With Mild/Moderate Disease According to The Clinical Global Impressions-Severity (CGI-S) Scale
时间窗: End of 2-week treatment period
Item 1 of the OHSA asked the patient to rate, using a 0-10 scale (0 meaning not bothered and 10 meaning the worst), his or her impression of the severity of dizziness, lightheadedness, feeling faint, or feeling like you might black out whenever he or she was standing and that improved when he or she sat or laid down. The results are reported by degree of severity according to the CGI-S scale, which uses 4 categories to describe disease severity: Mild, Moderate, Marked, and Severe. The Item 1 scores reported are grouped for participants with Mild or Moderate disease severity. Higher scores indicate more severe disease.
Re-analysis of The Post-treatment Score For Item 1 of The OHSA Scale, Excluding Two Sites
时间窗: End of 2-week treatment period
Item 1 of the OHSA asked the patient to rate, using a 0-10 scale (0 meaning not bothered and 10 meaning the worst), his or her impression of the severity of dizziness, lightheadedness, feeling faint, or feeling like you might black out whenever he or she was standing and that improved when he or she sat or laid down. Higher scores indicate more severe disease.
Post-treatment OHSA Item 1 Score of US Participants With Marked/Severe Disease According to The CGI-S Scale
时间窗: End of 2-week treatment period
Item 1 of the OHSA asked the patient to rate, using a 0-10 scale (0 meaning not bothered and 10 meaning the worst), his or her impression of the severity of dizziness, lightheadedness, feeling faint, or feeling like you might black out whenever he or she was standing and that improved when he or she sat or laid down. The results are reported by degree of severity according to the CGI-S scale, which uses 4 categories to describe disease severity: Mild, Moderate, Marked, and Severe. The Item 1 scores reported are grouped for participants with Marked or Severe disease severity. Higher scores indicate more severe disease.
次要结局
- Change From Baseline in The OHSA Composite Symptom Score(From the time of titration until the end of treatment)
- Change From Baseline in The OHSA Items 2 Through 6 Scores(From the time of titration until the end of treatment)
- Change From Baseline in The Orthostatic Hypotension Daily Activity Scale (OHDAS) Items 1 Through 4 Scores(From the time of titration until the end of treatment)
- Percent of Participants Scored as Improved on The Clinician Version of The Clinical Global Impressions Improvement (CGI-I) Scale(From the time of titration until the end of treatment)
- Change From Baseline in The Orthostatic Hypotension Global Daily Activity Score(From the time of titration until the end of treatment)
- Change From Baseline in Standing Blood Pressure (BP)(From the time of titration until the end of treatment)
- Change From Baseline in Supine BP(From the time of titration until the end of treatment)
- Change From Baseline in Short Form-36 (SF-36) Version 2 Health Survey Questionnaire Scores(From the time of titration until the end of treatment)
- Percent of Participants Scored as Improved on The Patient Version of The CGI-I Scale(From the time of titration until the end of treatment)
- Responsiveness of the Intent-to-Treat (ITT) Population(From the time of titration until the end of treatment)
- Convergent Validity of the Intent-to-Treat (ITT) Population(From the time of titration until the end of treatment)
- Test Reliability of the Intent-to-Treat (ITT) Population(From the time of titration until the end of treatment)