Comparision of Blood Pressure Variability Between Amlodipine and Losartan

NCT01964079 | Completed Phase 4 DMC

• 1 other identifier: COMPASS-BPV
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• SD of visit-to-visit systolic blood pressure variability

  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.

  6 months

Secondary Outcomes (7)

• Central systolic blood pressure

  6 months

• Augmentation index of central blood pressure

  6 months

• Standard deviation of within-visit systolic blood pressure variability

  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

Other Outcomes (1)

• Safety outcome

  6 months

Study Arms (2)

CCB (amlodipine)

ACTIVE COMPARATOR

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.

Drug: Amlodipine

ARB (losartan)

ACTIVE COMPARATOR

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.

Drug: Losartan

Interventions

Amlodipine 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.

Also known as: Norvasc

CCB (amlodipine)

Losartan 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.

Also known as: Cozaar

ARB (losartan)

Eligibility Criteria

• Age: 20 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Wonju Severance Christian Hospital: lead
• Pfizer: collaborator

Study Sites (1)

Wonju Severance Christian Hospital

Wŏnju, Gangwon-do, 220-701, South Korea

Location

MeSH Terms

Conditions

Hypertension

Interventions

Amlodipine; Losartan

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Tetrazoles

Study Officials

• Byung-Su Yoo, MD, PhD

  Wonju Severance Christian Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 10, 2013
• First Posted: October 17, 2013
• Study Start: April 1, 2013
• Primary Completion: April 1, 2017
• Study Completion: May 1, 2017
• Last Updated: May 12, 2017

Record last verified: 2017-05

Locations

KR (1)