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 to reduce the incidence of cardiovascular events in Japanese elderly high-risk hypertensive patients not adequately controlled by standard dose ARB alone

Condition	Intervention	Phase
Aged Hypertension Diabetes Mellitus Type 2 Cardiovascular Diseases	Drug: Olmesartan medoxomil (drug)  Drug: Calcium channel blockers (amlodipine, azelnidipine) (drug)	Phase IV

Further Study Details: 

Primary Outcomes: 1) A composite of fatal and non-fatal cardiovascular events; (1) Cerebrovascular events (cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, stroke of ndetermined etiology and transient ischemic attack); (2) Coronary events (sudden death, myocardial infarction, angina pectoris, asymptomatic myocardial ischemia); (3) Heart failure; (4) Vascular events (aortic aneurysm, aortic dissection, and arteriosclerotic diseases); (5) Diabetic complications (nephropathy, retinopathy and neuropathy); (6) Renal dysfunction (doubling of serum creatinine, end stage renal diseases); 2) All cause mortality
Secondary Outcomes: 1) Development of each cardiovascular event; 2) Blood pressure change (SBP, DBP, MBP) at every observation point in the follow-up period; 3) Serious adverse events other than primary outcome events
Expected Total Enrollment:  1000

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.

Ages Eligible for Study:  65 Years   -   84 Years,  Genders Eligible for Study:  Both

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 (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)
• Proteinurea: ≥ +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

Please refer to this study by ClinicalTrials.gov identifier  NCT00134160

Hisao Ogawa, MD      81-96-373-5175    ogawah@kumamoto-u.ac.jp
Shokei Mitsuyama, MD      81-96-373-5082    kimmitsu@gpo.kumamot-u.ac.jp

Japan, Kumamoto
      Department of Cardiovascular Midicine Graduate School of Medical Science Kumamoto University, 1-1-1 Honjyo, Kumamoto-City,  Kumamoto,  860-8556,  Japan; Recruiting
Japan, Tokyo
      OSCAR-Study Data Center, ShinjukuParkTower30FN, 3-7-1 Nishi-Shinjuku, Shinjuku-ku,  Tokyo,  163-1030,  Japan; Not yet recruiting

Study chairs or principal investigators

Kikuo Arakawa, MD,  Study Chair,  Emeritus Professor Fukuoka University, Consultant, Ishihara Cardiovascular Clinic, Fukuoka, Japan   

Study ID Numbers:  15-April-2005
Last Updated:  August 26, 2005
Record first received:  August 22, 2005
ClinicalTrials.gov Identifier:  NCT00134160
Health Authority: Japan: Ministry of Health, Labor and Welfare
ClinicalTrials.gov processed this record on 2005-08-30