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

Study Overview
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Brief Summary
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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.

Official Title
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The Combination Therapy of Hypertension to Prevent Cardiovascular Events Trial

Conditions
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Cardiovascular Disease

Intervention / Treatment
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* Drug: Angiotensin receptor blockers
* Drug: β-blockers
* Drug: thiazide diuretics


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: angiotensin receptor blockers<br>benidipine+angiotensin receptor blockers, titlation scheme | Drug: Angiotensin receptor blockers<br>* benidipine+angiotensin receptor blocker, titlation scheme<br>* Other names: benidipine, angiotensin receptor blockers;|
| Active Comparator: β-blockers<br>benidipie+β-blockers, titlation scheme | Drug: β-blockers<br>* benidipine+β-blockers, titlation scheme<br>* Other names: benidipine, β-blockers;|
| Active Comparator: thiazide diuretics<br>benidipine+thiazide diuretics, titlation scheme | Drug: thiazide diuretics<br>* benidipie+thiazide diuretics, titlation scheme<br>* Other names: benidipie, thiazide diuretics;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality. |  | first event | 
| Death from cardiovascular events. |  | first event | 
| Fatal and non-fatal cardiovascular events. |  | first event | 
| Hospitalization due to heart failure. |  | first event | 
| New onset of diabetes mellitus. |  | first event | 
| Safety (adverse events and adverse drug reaction). |  | total number | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Multicenter clinical trial, PROBE, Combination therapy, Benidipine, Essential Hypertension