Carotid Plaque, Essential Hypertension
Conditions
Brief summary
Effect of olmesartan medoxomil (20-40 mg) on plaque regression in hypertensive patients with carotid atherosclerosis.
Interventions
DRUGAtenolol
Atenolol (ATE) 50 mg and/or 100 mg tablets, oral, once daily
DRUGolmesartan medoxomil
Olmesartan medoxomil (OM), 20 mg and/or 40 mg, oral, once daily
Sponsors
Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female Caucasian outpatients aged \> 40 years. * High BP defined as mean SeSBP/SeDBP ≥ 140/90 mmHg. * One or more of the following additional risk factors: * Smoking; * Dyslipidaemia (high-density lipoprotein (HDL)-cholesterol \< 0.9 mmol/L or low-density lipoprotein (LDL)-cholesterol \> 2.6 mmol/L, or triglycerides \> 1.7 mmol/L); * Left ventricular hypertrophy; * Cardio-cerebrovascular events \> 6 months ago; * Presence of target organ damage. * Non-calcified (not marked shadowing) plaque in the CC artery, in the internal carotid artery or the carotid bulb with a PV ≥ 0.040 cm³ (≥ 40 µL) according to the measurements of EUTARC.
Exclusion criteria
* Secondary or high grade hypertension including grade III hypertension (SeSBP of \> 180 mmHg or SeDBP of \> 105 mmHg). * Stroke, myocardial infarction within the previous 6 months. * Interventional or surgical vascular treatment within the previous 3 months. * Presence of significant narrowing of the aortic or bicuspid valve and severe obstruction of cardiac outflow (hypertrophic cardiomyopathy). * Symptomatic heart failure. * Diabetes. * Chronic obstructive pulmonary disease (COPD) or asthma. * Claudication intermittens stage II b or higher. * Clinical evidence of severe renal disease \[including renovascular occlusive disease, nephrectomy and/or renal transplant, creatinine clearance of \< 30 mL/min, macroalbuminuria (\> 300 mg albumin/24 hours or 300 µg albumin/mg creatinine)\]. * Treatment with angiotensin converting enzyme (ACE)-inhibitors or angiotensin-receptor blockers (ARBs) during last 3 months. * Start of treatment with a lipid-lowering agent or modification of dosage within last 3 months. * Electrocardiographic (ECG) evidence of 2nd or 3rd degree atrioventricular (AV) block, atrial fibrillation, cardiac arrhythmia (requiring therapy) or bradycardia (\< 50 beats/min at rest). * Known intolerance to study drugs. * Impaired liver function tests suggesting severe liver disorder. * Any life threatening disease. * Duplex sonographically determined stenosis of the common or internal carotid artery \> 75%. * Plaque with marked shadowing from calcification. * Target plaques in CC artery extending into both internal and external arteries. * Pregnant or lactating female subjects. * Female subjects of childbearing potential without adequate contraception: intra-uterine devices, hormonal contraceptives, either oral, depot, patch or injectable and double barrier methods such as condoms or diaphragms with spermicidal gel or foam. If a female becomes pregnant during the trial, she has to be withdrawn immediately (see section 9.4). * Subject is currently enrolled in or has not yet completed at least 30 days since ending another investigational device or drug study or is receiving other investigational agents. * Subject has previously entered this study. * Subjects who have received ATE within 30 days prior to entering the active treatment phase. * Subjects who are unwilling or unable to provide informed consent or to participate satisfactorily for the entire trial period. * Subjects with history of alcohol and or drug abuse. * Subjects with known malabsorption syndrome. * Subjects who had donated or lost 450 mL or more blood during the last three months before Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in carotid plaque volume | 78 weeks (week 78 - week 0) | change in carotid plaque volume (PV) from baseline (week 0) as assessed by 3-D ultrasonography after 78 weeks of double-blind treatment with Olmesartan (OM) 20-40 mg daily compared to Atenololo (ATE) 50-100 mg daily (week 78 - week 0). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage changes of PV from baseline to Week 52 for olmesartan versus atenolol. | 52 weeks (week 52-week 0) | Determine the percentage changes of PV from baseline (week 0) to Week 52 for olmesartan versus atenolol. |
| Percentage changes of PV from baseline to Week 78 for olmesartan versus atenolol. | 78 weeks (week 78 - week 0) | Determine the percentage changes of PV from baseline (Week 0) to Week 78 for olmesartan versus atenolol. |
| Change in seated diastolic blood pressure (SeDBP) from baseline to Week 52 for olmesartan versus atenolol. | 52 weeks (week 52 - week 0) | Determine the change in seated diastolic blood pressure (SeDBP) from baseline (week 0) to Week 52 for olmesartan versus atenolol. |
| Change in seated diastolic blood pressure (SeDBP) from baseline to Week 78 for olmesartan versus atenolol. | 78 weeks (week 78 - week 0) | Determine the change in seated diastolic blood pressure (SeDBP) from baseline (week 0) to Week 78 for olmesartan versus atenolol. |
| Change in seated systolic blood pressure (SeSBP) from baseline to Week 52 for olmesartan versus atenolol. | 52 weeks (week 52 - week 0) | Determine the change in seated systolic blood pressure (SeSBP) from baseline (week 0)to Week 52 for olmesartan versus atenolol. |
| Change in plaque volume after 52 weeks, olmesartan versus atenolol | 52 weeks (week 52 - week 0) | change in plaque volume PV from baseline (week 0) to Week 52 on olmesartan therapy versus atenolol therapy |
| Change in PV from baseline to Week 52 after adjustments for changes in SeDBP from baseline. | 52 weeks (week 52 - week 0) | Determine the change in PV from baseline (week 0) to Week 52 after adjustments for changes in SeDBP from baseline. |
| Change in PV from baseline to Week 78 after adjustments for changes in SeDBP from baseline. | 78 weeks (Week 78 - week 0) | Determine the change in PV from baseline (week 0) to Week 78 after adjustments for changes in SeDBP from baseline. |
| Change in PV from baseline to Week 52 after adjustments for changes in SeSBP from baseline. | 52 weeks (week 52 - week 0) | Determine the change in PV from baseline (week 0) to Week 52 after adjustments for changes in SeSBP from baseline. |
| Change in PV from baseline to Week 78 after adjustments for changes in SeSBP from baseline. | 78 weeks (Week 78- week 0) | Determine the change in PV from baseline (week 0) to Week 78 after adjustments for changes in SeSBP from baseline. |
| Change in seated systolic blood pressure (SeSBP) from baseline to Week 78 for olmesartan versus atenolol. | 78 weeks (week 78 - week 0) | Determine the change in seated systolic blood pressure (SeSBP) from baseline (week 0) to Week 78 for olmesartan versus atenolol. |
Countries
Italy
Outcome results
None listed