Clinical trial NCT01964079: Comparision of Blood Pressure Variability Between Amlodipine and Losartan
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Lead sponsor: Wonju Severance Christian Hospital
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2013-10-17
Enrollment: 144
Sex: ALL
Minimum age (years): 20
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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.

  1. Hypertension and spontaneous or low-dose diuretic-induced hypokalemia.
  2. Drug-resistant hypertension, defined as sub-optimally controlled hypertension on a 3-drug program that includes an adrenergic inhibitor, vasodilator, and diuretic.
  3. Hypertension with adrenal incidentaloma.
  4. Hypertension and a family history of early-onset hypertension or cerebrovascular accident at a young age (\<40 years).
  5. 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.

Primary outcomes:
measure: SD of visit-to-visit systolic blood pressure variability
timeFrame: 6 months
Secondary outcomes:
measure: Central systolic blood pressure
timeFrame: 6 months
measure: Augmentation index of central blood pressure
timeFrame: 6 months
measure: Standard deviation of within-visit systolic blood pressure variability
timeFrame: 6 months
measure: Coefficient of variation of visit-to-visit systolic blood pressure variability
timeFrame: 6 months
measure: Variation independent of the mean of visit-to-visit systolic blood pressure variability
timeFrame: 6 months
measure: 24-h ambulatory blood pressure monitoring
timeFrame: 6 months
measure: Home systolic blood pressure
timeFrame: 6 months
Other outcomes:
measure: Safety outcome
timeFrame: 6 months
Locations:
city: Wonju
country: Korea, Republic of
facility: Wonju Severance Christian Hospital
state: Gangwon-do
Study officials:
affiliation: Wonju Severance Christian Hospital
name: Byung-Su Yoo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: