The Confirmatory Olmesartan Plaque Regression Study

Study Overview
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Brief Summary
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Effect of olmesartan medoxomil (20-40 mg) on plaque regression in hypertensive patients with carotid atherosclerosis.

Official Title
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Effects of Angiotensin-Receptor Blockade With Olmesartan on Carotid Atherosclerosis in Patients With Hypertension: The Confirmatory Olmesartan Plaque Regression Study

Conditions
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Essential Hypertension, Carotid Plaque

Intervention / Treatment
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* Drug: Atenolol
* Drug: olmesartan medoxomil


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Atenolol<br>Atenolol (ATE) 50 mg and/or 100 mg tablets, oral, once daily. | Drug: Atenolol<br>* Atenolol (ATE) 50 mg and/or 100 mg tablets, oral, once daily<br>|
| Experimental: Olmesartan medoxomil<br>Olmesartan medoxomil (OM), 20 mg and/or 40 mg, oral, once daily. | Drug: olmesartan medoxomil<br>* Olmesartan medoxomil (OM), 20 mg and/or 40 mg, oral, once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in carotid plaque volume | 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). | 78 weeks (week 78 - week 0) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plaque volume after 52 weeks, olmesartan versus atenolol | change in plaque volume PV from baseline (week 0) to Week 52 on olmesartan therapy versus atenolol therapy | 52 weeks (week 52 - week 0) | 
| Percentage changes of PV from baseline to Week 52 for olmesartan versus atenolol. | Determine the percentage changes of PV from baseline (week 0) to Week 52 for olmesartan versus atenolol. | 52 weeks (week 52-week 0) | 
| Percentage changes of PV from baseline to Week 78 for olmesartan versus atenolol. | Determine the percentage changes of PV from baseline (Week 0) to Week 78 for olmesartan versus atenolol. | 78 weeks (week 78 - week 0) | 
| Change in seated diastolic blood pressure (SeDBP) from baseline to Week 52 for olmesartan versus atenolol. | Determine the change in seated diastolic blood pressure (SeDBP) from baseline (week 0) to Week 52 for olmesartan versus atenolol. | 52 weeks (week 52 - week 0) | 
| Change in seated diastolic blood pressure (SeDBP) from baseline to Week 78 for olmesartan versus atenolol. | Determine the change in seated diastolic blood pressure (SeDBP) from baseline (week 0) to Week 78 for olmesartan versus atenolol. | 78 weeks (week 78 - week 0) | 
| Change in seated systolic blood pressure (SeSBP) from baseline to Week 52 for olmesartan versus atenolol. | Determine the change in seated systolic blood pressure (SeSBP) from baseline (week 0)to Week 52 for olmesartan versus atenolol. | 52 weeks (week 52 - week 0) | 
| Change in seated systolic blood pressure (SeSBP) from baseline to Week 78 for olmesartan versus atenolol. | Determine the change in seated systolic blood pressure (SeSBP) from baseline (week 0) to Week 78 for olmesartan versus atenolol. | 78 weeks (week 78 - week 0) | 
| Change in PV from baseline to Week 52 after adjustments for changes in SeDBP from baseline. | Determine the change in PV from baseline (week 0) to Week 52 after adjustments for changes in SeDBP from baseline. | 52 weeks (week 52 - week 0) | 
| Change in PV from baseline to Week 78 after adjustments for changes in SeDBP from baseline. | Determine the change in PV from baseline (week 0) to Week 78 after adjustments for changes in SeDBP from baseline. | 78 weeks (Week 78 - week 0) | 
| Change in PV from baseline to Week 52 after adjustments for changes in SeSBP from baseline. | Determine the change in PV from baseline (week 0) to Week 52 after adjustments for changes in SeSBP from baseline. | 52 weeks (week 52 - week 0) | 
| Change in PV from baseline to Week 78 after adjustments for changes in SeSBP from baseline. | Determine the change in PV from baseline (week 0) to Week 78 after adjustments for changes in SeSBP from baseline. | 78 weeks (Week 78- week 0) |