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

NCT00135551 | Completed Phase 4 DMC

• 1 other identifier: copeadministrator
• Study Type: interventional
• Target: 3,501
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiovascular Disease

Keywords

Hypertension; Multicenter clinical trial; PROBE; Combination therapy; Benidipine; Essential Hypertension

Outcome Measures

Primary Outcomes (2)

• A composite of fatal and non-fatal cardiovascular events.

  first event

• Achievement of target blood pressure (< 140 mmHg/90 mmHg).

  time course

Secondary Outcomes (6)

• 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

Study Arms (3)

angiotensin receptor blockers

ACTIVE COMPARATOR

benidipine+angiotensin receptor blockers, titlation scheme

Drug: Angiotensin receptor blockers

β-blockers

ACTIVE COMPARATOR

benidipie+β-blockers, titlation scheme

Drug: β-blockers

thiazide diuretics

ACTIVE COMPARATOR

benidipine+thiazide diuretics, titlation scheme

Drug: thiazide diuretics

Interventions

Angiotensin receptor blockers DRUG

benidipine+angiotensin receptor blocker, titlation scheme

Also known as: benidipine, angiotensin receptor blockers

angiotensin receptor blockers

β-blockers DRUG

benidipine+β-blockers, titlation scheme

Also known as: benidipine, β-blockers

β-blockers

thiazide diuretics DRUG

benidipie+thiazide diuretics, titlation scheme

Also known as: benidipie, thiazide diuretics

thiazide diuretics

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Seiji Umemoto, M.D., Ph.D.: lead
• The Japanese Society of Hypertension: collaborator
• Yamaguchi University Hospital: collaborator
• Kyowa Hakko Kogyo Co., Ltd.: collaborator

Study Sites (1)

Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine

Ube, Yamaguchi, 755-8505, Japan

Location

Related Publications (6)

• 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. doi: 10.1291/hypres.28.331.

  PMID: 16138563 BACKGROUND

• 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. Prevention of cardiovascular events with calcium channel blocker-based combination therapies in patients with hypertension: a randomized controlled trial. J Hypertens. 2011 Aug;29(8):1649-59. doi: 10.1097/HJH.0b013e328348345d.

  PMID: 21610513 RESULT

• 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 hypertension in the elderly: a sub-analysis of the Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) Trial. Hypertens Res. 2012 Apr;35(4):441-8. doi: 10.1038/hr.2011.216. Epub 2012 Jan 26.

  PMID: 22278623 RESULT

• Umemoto S, Ogihara T, Matsuzaki M, Rakugi H, Shimada K, Hayashi K, Makino H, Ohashi Y, Saruta T. Effects of an Antihypertensive Combination in Japanese Hypertensive Outpatients Based on the Long-acting Calcium Channel Blocker Benidipine on Vascular and Renal Events: A Sub-analysis of the COPE Trial. Curr Hypertens Rev. 2020;16(3):238-245. doi: 10.2174/1573402116666200129130151.

  PMID: 31995012 DERIVED

• Umemoto S, Ogihara T, Matsuzaki M, Rakugi H, Ohashi Y, Saruta T; Combination Therapy of Hypertension to Prevent Cardiovascular Events COPE Trial Group. Effects of calcium channel blocker-based combinations on intra-individual blood pressure variability: post hoc analysis of the COPE trial. Hypertens Res. 2016 Jan;39(1):46-53. doi: 10.1038/hr.2015.104. Epub 2015 Oct 22.

  PMID: 26490089 DERIVED

• Umemoto S, Ogihara T, Rakugi H, Matsumoto M, Kitagawa K, Shimada K, Higaki J, Ito S, Suzuki H, Ohashi Y, Saruta T, Matsuzaki M; Combination Therapy of Hypertension to Prevent Cardiovascular. Effects of a benidipine-based combination therapy on the risk of stroke according to stroke subtype: the COPE trial. Hypertens Res. 2013 Dec;36(12):1088-95. doi: 10.1038/hr.2013.100. Epub 2013 Aug 29.

  PMID: 23985703 DERIVED

Related Links

• Japanese Society of Hypertension
• Department of Geriatric Medicine, Osaka University Graduate School of Medicine

MeSH Terms

Conditions

Cardiovascular Diseases; Hypertension; Essential Hypertension

Interventions

Angiotensin Receptor Antagonists; benidipine; Sodium Chloride Symporter Inhibitors

Condition Hierarchy (Ancestors)

Vascular Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Membrane Transport Modulators; Diuretics; Natriuretic Agents; Physiological Effects of Drugs

Study Officials

• Toshio Ogihara, MD, PhD

  Department of Geriatric Medicine, Osaka University Graduate School of Medicine

  PRINCIPAL INVESTIGATOR

• Takao Saruta, MD, PhD

  Department of Internal Medicine, Keio University School of Medicine

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 24, 2005
• First Posted: August 26, 2005
• Study Start: May 1, 2003
• Primary Completion: May 1, 2010
• Study Completion: November 1, 2010
• Last Updated: February 22, 2012

Record last verified: 2012-02

Locations

JP (1)