The COMPAriSon of Systolic Blood Pressure Variability and Central Blood Pressure of Calcium Channel Blocker (Amlodipine) in Comparison With Angiotensin Receptor Blocker (Losartan) in Patients With Essential Hypertension
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 144
- 试验地点
- 1
- 主要终点
- SD of visit-to-visit systolic blood pressure variability
研究概览
简要总结
Blood pressure (BP) is believed to be a major determinant of vascular disease, and BP lowering is the most important goal in hypertension treatment. Thus, clinical guidelines for hypertension are mainly focused on lowering mean BP. However, despite an increasing incidence of stroke with age, the association between systolic BP (SBP) and the risk of stroke decreases with age. This disparity highlights a gap in the link between BP and vascular-related diseases (i.e., stroke). In clinical practice, visit-to-visit fluctuations in BP have been largely ignored and are thought to be an unreliable finding, even though this phenomenon is frequently observed. Rothwell et al. demonstrated that the visit-to-visit variability in SBP was a more powerful independent predictor of stroke than mean SBP, and that an increased residual variability in SBP in treated hypertensive patients was also a strong predictor of stroke and coronary events.
Recently updated (2011) hypertension guidelines from the National Institute for Health and Clinical Excellence (NICE) recommend an angiotensin converting enzyme inhibitor (ACEi) [or angiotensin II receptor blocker (ARB)] and calcium-channel blocker (CCB) as a first line drug. Although the significance of BP variability (BPV) has been illustrated, the main focus of the current guidelines is to reduce systolic and diastolic BP, not BPV.
In the X-CELLENT study, a CCB (amlodipine) and thiazide-like diuretic drug (indapamide sustained-release) led to a significant reduction in BPV, compared to an ARB (candesartan). In addition, the CCB showed the most effective reduction in systolic BPV among the antihypertensive drug class in a meta-analysis. However, there are no direct comparison studies of a CCB and ARB on BPV. Thus, we aim to compare the systolic BPV effects of a CCB versus an ARB in essential hypertensive patients. The primary hypothesis is that an ARB is not inferior to a CCB in the reduction of the systolic BPV standard deviation (SD) in essential hypertensive patients.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 20 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 20 years or older and below 80 years.
- •Patients who have not previously taken any antihypertensive drugs or have discontinued previous antihypertensive drugs for 2 weeks.
- •Mean SBP ≥140 mmHg or mean diastolic BP ≥ 90 mmHg (blood pressure will be checked at least 2 times in a seated position during the screening period).
排除标准
- •Pregnant women, possible candidate for pregnancy, or breastfeeding women.
- •Known or suspected secondary hypertension.
- •Mean seated SBP ≥ 180 mmHg and/or mean seated diastolic BP ≥ 120 mmHg at any visit.
- •Any clinically significant hepatic impairments.
- •Severe renal impairment (serum creatinine level > 3.0 mg/dL or creatinine clearance < 30 mL/min).
- •Bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, or post-renal transplant.
- •Clinically relevant hyperkalemia.
- •Uncorrected volume or sodium depletion.
- •Suspected primary aldosteronism.
- •Hypertension and spontaneous or low-dose diuretic-induced hypokalemia.
- •Drug-resistant hypertension, defined as sub-optimally controlled hypertension on a 3-drug program that includes an adrenergic inhibitor, vasodilator, and diuretic.
- •Hypertension with adrenal incidentaloma.
- •Hypertension and a family history of early-onset hypertension or cerebrovascular accident at a young age (<40 years).
- •Hypertensive first-degree relatives of patients with primary aldosteronism.
- •Symptomatic congestive heart failure.
- •Angina pectoris requiring treatment.
- •History of myocardial infarction or cerebrovascular accident (ischemic stroke or hemorrhage).
- •History of refractory or potentially lethal arrhythmias.
- •Concurrent participation in another clinical trial.
- •Patients with known intolerance, contraindication, or hypersensitivity to any component of dihydropyridines or angiotensin II receptor blockers.
- •Patients who are deemed unsuitable by the investigator.
研究组 & 干预措施
CCB (amlodipine)
For patients who fail to respond to 5 mg oral amlodipine daily, the dose will be titrated up to 10 mg amlodipineh. At subsequent visits, additional antihypertensive therapy (hydrochlorothiazide) will be added if systolic (>140 mmHg) or diastolic (>90 mmHg) BP is inadequate. Study drugs are administered once a day for 24 weeks. The dose will be titrated up if SBP is over 90 mmHg or there are no symptoms of hypotension (syncope, loss of consciousness, or orthostatic hypotension). If up-titration is not tolerable, because of side effects or hypotension, the previous dose will be administered as the final tolerable dose.
干预措施: Amlodipine (Drug)
ARB (losartan)
For patients who fail to respond to 50 mg oral losartan daily, the dose will be titrated up to 100 mg losartan. At subsequent visits, additional antihypertensive therapy (hydrochlorothiazide) will be added if systolic (>140 mmHg) or diastolic (>90 mmHg) BP is inadequate. Study drugs are administered once a day for 24 weeks. The dose will be titrated up if SBP is over 90 mmHg or there are no symptoms of hypotension (syncope, loss of consciousness, or orthostatic hypotension). If up-titration is not tolerable, because of side effects or hypotension, the previous dose will be administered as the final tolerable dose.
干预措施: Losartan (Drug)
结局指标
主要结局
SD of visit-to-visit systolic blood pressure variability
时间窗: 6 months
Consecutive measured blood pressure values from each visit will be averaged, and the standard deviation (SD) is calculated using the mean systolic blood pressure of each visit.
次要结局
- Augmentation index of central blood pressure(6 months)
- 24-h ambulatory blood pressure monitoring(6 months)
- Central systolic blood pressure(6 months)
- Coefficient of variation of visit-to-visit systolic blood pressure variability(6 months)
- Variation independent of the mean of visit-to-visit systolic blood pressure variability(6 months)
- Standard deviation of within-visit systolic blood pressure variability(6 months)
- Home systolic blood pressure(6 months)
研究者
Byung-Su Yoo
Professor
Wonju Severance Christian Hospital