Cardiovascular Disease
Conditions
Keywords
Hypertension, Multicenter clinical trial, PROBE, Combination therapy, Benidipine, Essential Hypertension
Brief summary
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.
Interventions
benidipine+angiotensin receptor blocker, titlation scheme
DRUGβ-blockers
benidipine+β-blockers, titlation scheme
benidipie+thiazide diuretics, titlation scheme
Sponsors
The Japanese Society of Hypertension
Yamaguchi University Hospital
Kyowa Hakko Kogyo Co., Ltd.
Seiji Umemoto, M.D., Ph.D.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Outpatients who are required a combination therapy with sitting systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg. * Outpatients aged over 40 years and less than 85 years (inclusive), regardless of sex. * Previously untreated patients or patients who are on other therapy, which can be converted to 4mg of benidipine. * Patients who can be treated with benidipine, angiotensin receptor blockers, β-blockers, and thiazide diuretics.
Exclusion criteria
* Seated systolic blood pressure ≥ 200 mmHg or seated diastolic blood pressure ≥ 120 mmHg. * Secondary hypertension. * Type I diabetes mellitus or type 2 diabetes on insulin treatment. * 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. * Heart failure (New York Heart Association \[NYHA\] functional classification II, III or IV). * Chronic atrial fibrillation or atrial flutter. * Congenital heart disease or a history of rheumatic heart disease. * Severe peripheral arterial disease (Fontaine Class II, III or IV). * Serious liver dysfunction (AST or ALT ≥100 IU / l). * Serious renal dysfunction (serum creatinine ≥ 2mg/dl). * History of malignancy 5 years prior to study entry. * Pregnancy. * Compliance rate \< 70% assessed by a patient interview. * Known hypersensitivity or contraindication to benidipine, angiotensin receptor blockers, β-blockers, and thiazide diuretics. * Other serious illness or significant abnormalities that the investigator judges inappropriate for the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| A composite of fatal and non-fatal cardiovascular events. | first event |
| Achievement of target blood pressure (< 140 mmHg/90 mmHg). | time course |
Secondary
| Measure | Time frame |
|---|---|
| Fatal and non-fatal cardiovascular events. | first event |
| Hospitalization due to heart failure. | first event |
| All-cause mortality. | first event |
| Safety (adverse events and adverse drug reaction). | total number |
| New onset of diabetes mellitus. | first event |
| Death from cardiovascular events. | first event |
Countries
Japan
Outcome results
None listed