Clinical trial NCT01132768: The Confirmatory Olmesartan Plaque Regression Study
Official title: Effects of Angiotensin-Receptor Blockade With Olmesartan on Carotid Atherosclerosis in Patients With Hypertension: The Confirmatory Olmesartan Plaque Regression Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Essential Hypertension
Carotid Plaque
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2010-05-28
Enrollment: 114
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Change in carotid plaque volume
timeFrame: 78 weeks (week 78 - week 0)
Secondary outcomes:
measure: Change in plaque volume after 52 weeks, olmesartan versus atenolol
timeFrame: 52 weeks (week 52 - week 0)
measure: Percentage changes of PV from baseline to Week 52 for olmesartan versus atenolol.
timeFrame: 52 weeks (week 52-week 0)
measure: Percentage changes of PV from baseline to Week 78 for olmesartan versus atenolol.
timeFrame: 78 weeks (week 78 - week 0)
measure: Change in seated diastolic blood pressure (SeDBP) from baseline to Week 52 for olmesartan versus atenolol.
timeFrame: 52 weeks (week 52 - week 0)
measure: Change in seated diastolic blood pressure (SeDBP) from baseline to Week 78 for olmesartan versus atenolol.
timeFrame: 78 weeks (week 78 - week 0)
measure: Change in seated systolic blood pressure (SeSBP) from baseline to Week 52 for olmesartan versus atenolol.
timeFrame: 52 weeks (week 52 - week 0)
measure: Change in seated systolic blood pressure (SeSBP) from baseline to Week 78 for olmesartan versus atenolol.
timeFrame: 78 weeks (week 78 - week 0)
measure: Change in PV from baseline to Week 52 after adjustments for changes in SeDBP from baseline.
timeFrame: 52 weeks (week 52 - week 0)
measure: Change in PV from baseline to Week 78 after adjustments for changes in SeDBP from baseline.
timeFrame: 78 weeks (Week 78 - week 0)
measure: Change in PV from baseline to Week 52 after adjustments for changes in SeSBP from baseline.
timeFrame: 52 weeks (week 52 - week 0)
measure: Change in PV from baseline to Week 78 after adjustments for changes in SeSBP from baseline.
timeFrame: 78 weeks (Week 78- week 0)
Other outcomes:
Locations:
city: Sesto Fiorentino
country: Italy
Study officials:
affiliation: Centre of Preventative Medicine
name: Klaus O Stumpe, MD
role: PRINCIPAL_INVESTIGATOR
References: