A number of major clinical trials have demonstrated the clinical benefits of lowering blood pressure and have indicated that a majority of patients with hypertension will require more than one drug to achieve optimal blood pressure control.

There is little data showing which antihypertensive combination best protects patients from cardiovascular events and which best achieves the target blood pressure with the fewest adverse events.

The COPE trial is planned to investigate, in patients with hypertension, which combination of the antihypertensive drugs; angiotensin receptor blockers, β-blockers or thiazide diuretics in addition to a long-acting calcium antagonist, benidipine hydrochloride, is superior to achieve the targeted blood pressure and prevent cardiovascular events with the fewest adverse drug effects.

Condition	Intervention	Phase
Essential Hypertension Cardiovascular Disease	Drug: Benidipine hydrochloride  Drug: Angiotensin receptor blockers  Drug: β-blockers  Drug: Thiazide diuretics	Phase III

Further Study Details: 

Primary Outcomes: 1) A composite of fatal and non-fatal cardiovascular events; 1. Sudden death (acute onset and intrinsic death within 24 h).; 2. Fatal or nonfatal stroke (new onset or recurrence).; 3. Fatal or nonfatal myocardial infarction (new onset or recurrence), hospitalization due to unstable angina, new onset of heart failure (Class II, III, or IV), sudden cardiac death.; 4. New onset or worsening of peripheral arterial disease.; 5. New onset or worsening of renal failure (as indicated by a serum creatinine level that is at least doubled to over 2 mg/dl), serum creatinine ≥ 4.0 mg/dl, renal dialysis or renal transplantation.; 2) Achievement of target blood pressure (systolic blood pressure < 140 mmHg and diastolic blood pressure <90 mmHg).
Secondary Outcomes: 1. All-cause mortality.; 2. Death from cardiovascular events.; 3. Fatal and non-fatal cardiovascular events.; 4. Hospitalization due to heart failure.; 5. New onset of diabetes mellitus.; 6. Safety (adverse events and adverse drug reaction).
Expected Total Enrollment:  3000

Ages Eligible for Study:  40 Years   -   85 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

1. Outpatients who are required a combination therapy with sitting systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg.
2. Outpatients aged over 40 years and less than 85 years (inclusive), regardless of sex.
3. Previously untreated patients or patients who are on other therapy, which can be converted to 4mg of benidipine.
4. Patients who can be treated with benidipine, angiotensin receptor blockers, β-blockers, and thiazide diuretics.

Exclusion Criteria:

1. Seated systolic blood pressure ≥ 200 mmHg or seated diastolic blood pressure ≥ 120 mmHg.
2. Secondary hypertension.
3. Type I diabetes mellitus or type 2 diabetes on insulin treatment.
4. History of cerebrovascular disorder, myocardial infarction, angina pectoris, coronary angioplasty or coronary artery bypass graft surgery within 6 months prior to enrolment in the study.
5. Heart failure (NYHA functional classification II, III or IV).
6. Chronic atrial fibrillation or atrial flutter.
7. Congenital heart disease or a history of rheumatic heart disease.
8. Severe peripheral arterial disease (Fontaine Class II, III or IV).
9. Serious liver dysfunction (AST or ALT ≥100 IU / l).
10. Serious renal dysfunction (serum creatinine ≥ 2mg/dl).
11. History of malignancy 5 years prior to study entry.
12. Pregnancy.
13. Compliance rate < 70% assessed by a patient interview.
14. Known hypersensitivity or contraindication to benidipine, angiotensin receptor blockers, β-blockers, and thiazide diuretics.
15. Other serious illness or significant abnormalities that the investigator judges inappropriate for the study

Please refer to this study by ClinicalTrials.gov identifier  NCT00135551

Masunori Matsuzaki, MD, PhD      +81-836-22-2248    masunori@yamaguchi-u.ac.jp
Seiji Umemoto, MD, PhD      +81-836-22-2663    cope@yamaguchi-u.ac.jp

Japan, Yamaguchi
      Department of Cardiovascular Medicine, Yamaguchi University Graduate School of Medicine, Ube,  Yamaguchi,  755-8505,  Japan; Recruiting

Study chairs or principal investigators

Toshio Ogihara, MD, PhD,  Principal Investigator,  Department of Geriatric Medicine, Osaka University Graduate School of Medicine   
Takao Saruta, MD, PhD,  Study Chair,  Department of Internal Medicine, Keio University School of Medicine   

Study ID Numbers:  copeadministrator
Last Updated:  August 25, 2005
Record first received:  August 24, 2005
ClinicalTrials.gov Identifier:  NCT00135551
Health Authority: Japan: Ministry of Health, Labor and Welfare
ClinicalTrials.gov processed this record on 2005-08-30