Benidipine-based Comparison of Angiotensin Receptors, β-blockers, or Thiazide Diuretics in Hypertensive Patients (COPE)

Seiji Umemoto, M.D., Ph.D.

Status and phase: Completed; Phase 4

Conditions: Cardiovascular Disease

Treatments: Drug: β-blockers; Drug: thiazide diuretics; Drug: Angiotensin receptor blockers

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00135551

copeadministrator

Details and patient eligibility

About

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.

Enrollment: 3,501 patients

Sex: All

Ages: 40 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3,501 participants in 3 patient groups

angiotensin receptor blockers

Active Comparator group

Description:

benidipine+angiotensin receptor blockers, titlation scheme

Treatment:

Drug: Angiotensin receptor blockers

β-blockers

Active Comparator group

Description:

benidipie+β-blockers, titlation scheme

Treatment:

Drug: β-blockers

thiazide diuretics

Active Comparator group

Description:

benidipine+thiazide diuretics, titlation scheme

Treatment:

Drug: thiazide diuretics