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

Cardiovascular Disease Clinical Trial

— COPE  

Official title:

The Combination Therapy of Hypertension to Prevent Cardiovascular Events Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00135551
• Other study ID #: copeadministrator
• Status: Completed
• Phase: Phase 4
• First received: August 24, 2005
• Last updated: February 19, 2012
• Start date: May 2003
• Est. completion date: November 2010

Study information

• Verified date: February 2012
• Source: COPE Trial Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3501
• Est. completion date: November 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 85 Years

Eligibility

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, ß-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, ß-blockers, and thiazide diuretics.

• Other serious illness or significant abnormalities that the investigator judges inappropriate for the study

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases

Intervention

Drug:
• Angiotensin receptor blockers
benidipine+angiotensin receptor blocker, titlation scheme
• ß-blockers
benidipine+ß-blockers, titlation scheme
• thiazide diuretics
benidipie+thiazide diuretics, titlation scheme

Locations

Country	Name	City	State
Japan	Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine	Ube	Yamaguchi

Sponsors (4)

Lead Sponsor	Collaborator
Seiji Umemoto, M.D., Ph.D.	Kyowa Hakko Kogyo Co., Ltd., The Japanese Society of Hypertension, Yamaguchi University Hospital

Country where clinical trial is conducted

Japan, 

References & Publications (3)

Matsuzaki M, Ogihara T, Umemoto S, Rakugi H, Matsuoka H, Shimada K, Abe K, Suzuki N, Eto T, Higaki J, Ito S, Kamiya A, Kikuchi K, Suzuki H, Tei C, Ohashi Y, Saruta T; Combination Therapy of Hypertension to Prevent Cardiovascular Events Trial Group. Preven — View Citation

Ogihara T, Matsuzaki M, Matsuoka H, Shimamoto K, Shimada K, Rakugi H, Umemoto S, Kamiya A, Suzuki N, Kumagai H, Ohashi Y, Takishita S, Abe K, Saruta T; COPE Trial Group. The combination therapy of hypertension to prevent cardiovascular events (COPE) trial: rationale and design. Hypertens Res. 2005 Apr;28(4):331-8. Review. — View Citation

Ogihara T, Matsuzaki M, Umemoto S, Rakugi H, Matsuoka H, Shimada K, Higaki J, Ito S, Kamiya A, Suzuki H, Ohashi Y, Shimamoto K, Saruta T; Combination Therapy of Hypertension to Prevent Cardiovascular Events Trial Group. Combination therapy for hypertensio — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	A composite of fatal and non-fatal cardiovascular events.		first event	Yes
Primary	Achievement of target blood pressure (< 140 mmHg/90 mmHg).		time course	Yes
Secondary	All-cause mortality.		first event	Yes
Secondary	Death from cardiovascular events.		first event	Yes
Secondary	Fatal and non-fatal cardiovascular events.		first event	Yes
Secondary	Hospitalization due to heart failure.		first event	Yes
Secondary	New onset of diabetes mellitus.		first event	Yes
Secondary	Safety (adverse events and adverse drug reaction).		total number	Yes

External Links

•   Click here for more information about this study (in Japanese): The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) Trial
•   Department of Geriatric Medicine, Osaka University Graduate School of Medicine
•   Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine