A Randomized Crossover Study of Propranolol Versus Ivabradine in Postural Tachycardia Syndrome (POTS)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Change in HR
研究概览
简要总结
1.0 BACKGROUND Postural tachycardia syndrome (POTS) is a disorder of chronic orthostatic intolerance characterized by symptoms of palpitations, lightheadedness, chest discomfort, shortness of breath, blurred vision, and mental clouding. These symptoms occur during standing and are associated with a marked increase in heart rate (HR) in the absence of hypotension, which typically resolve when sitting or lying down. Most importantly, POTS is associated with a very poor quality of life and significant functional disability. POTS patients commonly experience mental clouding ("brain fog") even while lying down or seated, which poses significant limitations to daily activities .
Unfortunately, there is a relative paucity in the literature assessing therapies for POTS patients. Given that excessive tachycardia on standing is a fundamental component of this syndrome, a handful of studies have evaluated medications that reduce HR. Ivabradine is newer drug that is a selective If channel blocker that reduces HR without affecting other cardiovascular functions.
2.0 RATIONALE / STUDY PURPOSE The investigators propose to compare the efficacy of propranolol and ivabradine on HR response to standing, and symptom burden in patients with POTS.
3.0 Study Design This will be a single-center double-blind placebo-controlled randomized crossover trial conducted in patients with POTS to compare effects of (1) oral ivabradine 5 mg bid plus placebo BID (to fill out a QID schedule); (2) oral propranolol 10 mg qid; and (3) oral placebo qid in POTS patients. After a baseline screening assessment following a washout period of 7 days, participants will be randomized to start with a 4-week course of either ivabradine, propranolol or placebo. The other two treatments will be given in separate 4-week courses with a 7-day washout period between phases, with each participant acting as his or her own control. At the end of each 4-week phase, participants will complete the symptom-rating and HRQOL questionnaires, and also undergo tilt table testing to assess the change in HR at 10 min with head up tilt.
Participants will undergo POTS testing at baseline and at the end of each 4-week treatment course. This will involve a total of 4 separate study visits.
详细描述
1.0 BACKGROUND Postural tachycardia syndrome (POTS) is a disorder of chronic orthostatic intolerance characterized by symptoms of palpitations, lightheadedness, chest discomfort, shortness of breath, blurred vision, and mental clouding. These symptoms occur during standing and are associated with a marked increase in heart rate (HR) in the absence of hypotension, which typically resolve when sitting or lying down. Most importantly, POTS is associated with a very poor quality of life and significant functional disability. POTS patients commonly experience mental clouding ("brain fog") even while lying down or seated, which poses significant limitations to daily activities .
Unfortunately, there is a relative paucity in the literature assessing therapies for POTS patients. Given that excessive tachycardia on standing is a fundamental component of this syndrome, a handful of studies have evaluated medications that reduce HR. In a randomized crossover study of 54 patients with POTS, low-dose propranolol (10-20 mg PO) was found to acutely reduce standing HR compared to placebo. Further, there was greater improvement in symptom burden (quantified using the Vanderbilt Orthostatic Symptom Score [VOSS]) from baseline to 2 hours in patients treated with propranolol compared to placebo.
Ivabradine is newer drug that is a selective If channel blocker that reduces HR without affecting other cardiovascular functions. In non-randomized reports, it has been shown to improve symptoms in patients with POTS. In a case series of 22 patients, approximately 60% of patients with POTS treated with ivabradine had symptom improvement
2.0 RATIONALE / STUDY PURPOSE Patients with POTS suffer great disability and currently used pharmacologic therapies require more rigorous study. Currently, there are no studies comparing the relative efficacy of propranolol and ivabradine in patients with POTS.
We propose to compare the efficacy of propranolol and ivabradine on HR response to standing, and symptom burden in patients with POTS. This would be the first study to compare the relative efficacy of ivabradine to propranolol in POTS. The results of this exploratory study may help inform design of a larger multicenter clinical trial investigating the use of ivabradine or propranolol in POTS over time. We will test the null hypothesis that the heart rate lowering response to ivabradine is not different than the heart lowering response of propranolol.
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
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Postural Tachycardia Syndrome
- •Age between 18-60 years
- •Men and women are eligible
- •Able and willing to provide informed consent
排除标准
- •Seated resting heart rate < 70 bpm in the absence of rate-lowering medications
- •Supine blood pressure < 90/60 mmHg
- •Overt cause for postural tachycardia, i.e., acute dehydration, prolonged bed rest
- •Presence of underlying structural heart disease including:
- •Valvular disease (i.e. moderate or greater valvular stenosis or regurgitation)
- •History of heart failure
- •Greater than mild left ventricular systolic impairment
- •Hypertrophic cardiomyopathy
- •Known coronary artery disease or prior myocardial infarction
- •History of tachyarrhythmias including:
- •Supraventricular tachycardia, atrial tachycardia, atrial fibrillation / flutter
- •Ventricular tachyarrhythmias
- •Pre-existing long QT interval (e.g. known congenital long QT syndrome, or QT interval >500 ms)
- •History of sick sinus syndrome or high degree AV block
- •Presence of a pacemaker, implantable cardioverter defibrillator or cardiac resynchronization therapy device
- •Diabetes mellitus or history of hypoglycemic episodes
- •History of bronchospasm or uncontrolled asthma
- •Pregnant (by history or serum test) or breast-feeding
- •Inability to safely withdraw from existing beta-blockers or ivabradine prior to the study day
- •Concomitant use of class I and III antiarrhythmic agents, or non-dihydropyridine calcium channel blockers
- •Concomitant use of strong cytochrome P450 3A4 (CYP 3A4) inhibitors
- •Severe hepatic impairment
- •Any contraindication to propranolol or ivabradine not specifically listed above as per the product monographs.
- •Unable to give informed consent
研究组 & 干预措施
1st drug Ivabradine
Patients will take Ivabradine first followed by Propranolol and Placebo
干预措施: Ivabradine 4-week course (Drug)
1st drug Ivabradine
Patients will take Ivabradine first followed by Propranolol and Placebo
干预措施: Propranolol 4-week course (Drug)
1st drug Ivabradine
Patients will take Ivabradine first followed by Propranolol and Placebo
干预措施: Placebo 4-week course (Drug)
2nd drug Ivabradine
Patients will take either Propranolol or placebo first and then Ivabradine
干预措施: Ivabradine 4-week course (Drug)
2nd drug Ivabradine
Patients will take either Propranolol or placebo first and then Ivabradine
干预措施: Propranolol 4-week course (Drug)
2nd drug Ivabradine
Patients will take either Propranolol or placebo first and then Ivabradine
干预措施: Placebo 4-week course (Drug)
3rd drug Ivabradine
Patients will take Propranolol and placebo first and then Ivabradine
干预措施: Ivabradine 4-week course (Drug)
3rd drug Ivabradine
Patients will take Propranolol and placebo first and then Ivabradine
干预措施: Propranolol 4-week course (Drug)
3rd drug Ivabradine
Patients will take Propranolol and placebo first and then Ivabradine
干预措施: Placebo 4-week course (Drug)
结局指标
主要结局
Change in HR
时间窗: 4 weeks
the ∆HR from supine to standing on head-up tilt at 10 minutes after the 4 weeks each of patient taking Ivabradine, Propranolol and Placebo
次要结局
- Vanderbilt Orthostatic Symptoms Score(4 weeks)