OlmeSartan and Calcium Antagonists Randomized (OSCAR) Study

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate whether high-dose angiotensin II receptor blocker (ARB) monotherapy or combination therapy with ARB and calcium channel blockers is more effective in reducing the incidence of cardiovascular events in Japanese elderly high-risk hypertensive patients not adequately controlled by standard dose ARB alone.

Detailed Description
-----------------
Hypertension is one of the major risk factors of cardiovascular diseases. It is also important for elderly hypertensive patients to strictly reduce their blood pressures to prevent cardiovascular events. Although angiotensin II receptor blockers (ARBs) are increasingly used in antihypertensive treatment recently, few studies have been performed in Japan to assess the difference between high-dose ARB monotherapy and combination therapy of ARB with calcium channel blocker (CCB) in prevention of cardiovascular diseases for patients whose blood pressure is not well controlled by ARB monotherapy. OSCAR-study is a multicenter, active-controlled, 2-arm parallel group comparison, prospective randomized open blinded end-point (PROBE) design study. The dose administered is olmesartan medoxomil 20mg/day as ARB monotherapy in the 'Step 1' period. If the blood pressure is not adequately controlled and treatment is well tolerated then the dose is changed to olmesartan medoxomil 40mg/day in the high-dose ARB monotherapy group, or olmesartan medoxomil 20mg/day and a CCB in the combination therapy group in the 'Step 2' period. At least 500 patients will be enrolled in each group, and the follow-up duration will be 3 years. The primary objective is to compare the incidence of a composite of fatal and non-fatal cardiovascular events, and all cause mortality between the two treatment groups.

Official Title
-----------------
The Study Comparing the Incidence of Cardiovascular Events Between High-dose ARB Monotherapy and Combination Therapy With ARB and Calcium Channel Blocker in Japanese Elderly Hypertensive Patients at High Cardiovascular Risk

Conditions
-----------------
Hypertension, Cardiovascular Diseases

Intervention / Treatment
-----------------
* Drug: Olmesartan medoxomil
* Drug: Calcium channel blockers (amlodipine, azelnidipine)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Outpatients aged 65 years or older, and less than 85 years (at the time of informed consent), regardless of sex Current antihypertensive treatment with monotherapy SBP ≥ 140mmHg or DBP ≥ 90mmHg in a sitting position on two measurements on two clinic visits At least one of the following risk factors: Diabetes mellitus Type 2; History of cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, or transient ischemic attack (more than 6 months before giving informed consent); Diagnosis of asymptomatic cerebrovascular disease; History of myocardial infarction (more than 6 months before giving informed consent); Diagnosis of angina pectoris or heart failure (New York Heart Association [NYHA] functional classification I or II); Diagnosis of left ventricular hypertrophy (thickness of the wall of interventricular septum ≥ 12mm on echocardiography or Sv1+Rv5 ≥ 35mm on electrocardiography before informed consent); Diagnosis of aortic aneurysm; History of aortic dissection (more than 6 months before giving informed consent); Diagnosis of arteriosclerotic peripheral arterial obstruction (Fontaine classification from 2 to 4); Serum creatinine: 1.2-2.5mg/dL (male); 1.0-2.5mg/dL (female); Proteinuria: ≥ +1 (or ≥ 0.3g/g･Cr. estimated from 24-hour urine collection or random urinary protein corrected by urine creatinine). Exclusion Criteria: Secondary hypertension or malignant hypertension Heart failure (NYHA functional classification III or IV) Required treatment for malignant tumor Serious liver or renal dysfunction (serum creatinine > 2.5mg/dL or with dialysis treatment) Not appropriate for change to the test drugs from current therapy for hypertension or coronary diseases (i.e. calcium channel blockers, β-blockers, thiazide diuretics, etc.) History of serious adverse drug reactions to angiotensin II receptor blockers or calcium channel blockers Patients with other serious reasons (i.e. illness, significant abnormalities, etc.) that investigators judge inappropriate for the study

Ages Eligible for Study
-----------------
Minimum Age: 65 Years
Maximum Age: 84 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>High-dose ARB monotherapy | Drug: Olmesartan medoxomil<br>* Olmesartan medoxomil 40mg/Day<br>|
| Active Comparator: 2<br>Combination therapy of ARB with Calcium Channel Blocker | Drug: Calcium channel blockers (amlodipine, azelnidipine)<br>* Olmesartan medoxomil 20mg/Day with Calcium channel blockers (amlodipine or azelnidipine)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A composite of fatal and non-fatal cardiovascular events: Cerebrovascular events (cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, stroke of undetermined etiology and transient ischemic attack) |  | 36 Months | 
| Coronary events (sudden death, myocardial infarction, angina pectoris, asymptomatic myocardial ischemia) |  | 36 Months | 
| Heart failure |  | 36 Months | 
| Vascular events (aortic aneurysm, aortic dissection, and arteriosclerotic diseases) |  | 36 Months | 
| Diabetic complications (nephropathy, retinopathy and neuropathy) |  | 36 Months | 
| Renal dysfunction (doubling of serum creatinine, end stage renal diseases) |  | 36 Months | 
| All cause mortality |  | 36 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of each cardiovascular event |  | 36 Months | 
| Blood pressure change (systolic blood pressure [SBP], diastolic blood pressure [DBP], mean blood pressure [MBP]) at every observation point in the follow-up period |  | 36 Months | 
| Serious adverse events other than primary outcome events |  | 36 Months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aged, Hypertension, Cardiovascular Diseases, Angiotensin II Type 1 Receptor Blockers, Calcium Channel Blockers, Combination Drug Therapy, Diabetes Mellitus Type 2