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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00135551
Recruitment Status : Completed
First Posted : August 26, 2005
Last Update Posted : February 22, 2012
The Japanese Society of Hypertension
Yamaguchi University Hospital
Kyowa Hakko Kogyo Co., Ltd.
Information provided by (Responsible Party):
Seiji Umemoto, M.D., Ph.D., COPE Trial Group

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.

Condition or disease Intervention/treatment Phase
Cardiovascular Disease Drug: Angiotensin receptor blockers Drug: β-blockers Drug: thiazide diuretics Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3501 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: The Combination Therapy of Hypertension to Prevent Cardiovascular Events Trial
Study Start Date : May 2003
Actual Primary Completion Date : May 2010
Actual Study Completion Date : November 2010

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: angiotensin receptor blockers
benidipine+angiotensin receptor blockers, titlation scheme
Drug: Angiotensin receptor blockers
benidipine+angiotensin receptor blocker, titlation scheme
Other Name: benidipine, angiotensin receptor blockers

Active Comparator: β-blockers
benidipie+β-blockers, titlation scheme
Drug: β-blockers
benidipine+β-blockers, titlation scheme
Other Name: benidipine, β-blockers

Active Comparator: thiazide diuretics
benidipine+thiazide diuretics, titlation scheme
Drug: thiazide diuretics
benidipie+thiazide diuretics, titlation scheme
Other Name: benidipie, thiazide diuretics

Primary Outcome Measures :
  1. A composite of fatal and non-fatal cardiovascular events. [ Time Frame: first event ]
  2. Achievement of target blood pressure (< 140 mmHg/90 mmHg). [ Time Frame: time course ]

Secondary Outcome Measures :
  1. All-cause mortality. [ Time Frame: first event ]
  2. Death from cardiovascular events. [ Time Frame: first event ]
  3. Fatal and non-fatal cardiovascular events. [ Time Frame: first event ]
  4. Hospitalization due to heart failure. [ Time Frame: first event ]
  5. New onset of diabetes mellitus. [ Time Frame: first event ]
  6. Safety (adverse events and adverse drug reaction). [ Time Frame: total number ]

Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00135551

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Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine
Ube, Yamaguchi, Japan, 755-8505
Sponsors and Collaborators
Seiji Umemoto, M.D., Ph.D.
The Japanese Society of Hypertension
Yamaguchi University Hospital
Kyowa Hakko Kogyo Co., Ltd.
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Principal Investigator: Toshio Ogihara, MD, PhD Department of Geriatric Medicine, Osaka University Graduate School of Medicine
Study Chair: Takao Saruta, MD, PhD Department of Internal Medicine, Keio University School of Medicine
Additional Information:
Publications of Results:
Other Publications:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Seiji Umemoto, M.D., Ph.D., Associate Professor, COPE Trial Group Identifier: NCT00135551    
Other Study ID Numbers: copeadministrator
First Posted: August 26, 2005    Key Record Dates
Last Update Posted: February 22, 2012
Last Verified: February 2012
Keywords provided by Seiji Umemoto, M.D., Ph.D., COPE Trial Group:
Multicenter clinical trial
Combination therapy
Essential Hypertension
Additional relevant MeSH terms:
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Cardiovascular Diseases
Angiotensin Receptor Antagonists
Sodium Chloride Symporter Inhibitors
Adrenergic beta-Antagonists
Natriuretic Agents
Physiological Effects of Drugs
Molecular Mechanisms of Pharmacological Action
Membrane Transport Modulators
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Calcium Channel Blockers
Calcium-Regulating Hormones and Agents
Vasodilator Agents