Comparision of Blood Pressure Variability Between Amlodipine and Losartan

NCT ID: NCT01964079

Last Updated: 2017-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 144 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2017-05-31

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.

Conditions

Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Amlodipine

Intervention Type: DRUG

Eligible subjects will be randomized 1:1 to either an amlodipine or a losartan group by a computer-generated random number table. For patients who fail to respond to 5 mg amlodipine, the dose will be titrated up to 10 mg amlodipine. 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.

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.

Group Type: ACTIVE_COMPARATOR

Losartan

Intervention Type: DRUG

Eligible subjects will be randomized 1:1 to either an amlodipine or a losartan group by a computer-generated random number table. For patients who fail to respond to 50 mg losartan, 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.

Interventions

Amlodipine

Eligible subjects will be randomized 1:1 to either an amlodipine or a losartan group by a computer-generated random number table. For patients who fail to respond to 5 mg amlodipine, the dose will be titrated up to 10 mg amlodipine. 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.

Intervention Type: DRUG

Losartan

Eligible subjects will be randomized 1:1 to either an amlodipine or a losartan group by a computer-generated random number table. For patients who fail to respond to 50 mg losartan, 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.

Intervention Type: DRUG

Other Intervention Names

Norvasc; Cozaar

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Wonju Severance Christian Hospital

OTHER

Sponsor Role: lead

Responsible Party

Byung-Su Yoo

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Byung-Su Yoo, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Wonju Severance Christian Hospital

Locations

Wonju Severance Christian Hospital

Wŏnju, Gangwon-do, South Korea

Countries

South Korea

Other Identifiers

COMPASS-BPV

Identifier Type: -

Identifier Source: org_study_id