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

This study has been completed.
Sponsor:
Collaborators:
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
ClinicalTrials.gov Identifier:
NCT00135551
First received: August 24, 2005
Last updated: February 19, 2012
Last verified: February 2012
  Purpose

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 Intervention Phase
Cardiovascular Disease
Drug: Angiotensin receptor blockers
Drug: β-blockers
Drug: thiazide diuretics
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: The Combination Therapy of Hypertension to Prevent Cardiovascular Events Trial

Resource links provided by NLM:


Further study details as provided by COPE Trial Group:

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

Secondary Outcome Measures:
  • All-cause mortality. [ Time Frame: first event ] [ Designated as safety issue: Yes ]
  • Death from cardiovascular events. [ Time Frame: first event ] [ Designated as safety issue: Yes ]
  • Fatal and non-fatal cardiovascular events. [ Time Frame: first event ] [ Designated as safety issue: Yes ]
  • Hospitalization due to heart failure. [ Time Frame: first event ] [ Designated as safety issue: Yes ]
  • New onset of diabetes mellitus. [ Time Frame: first event ] [ Designated as safety issue: Yes ]
  • Safety (adverse events and adverse drug reaction). [ Time Frame: total number ] [ Designated as safety issue: Yes ]

Enrollment: 3501
Study Start Date: May 2003
Study Completion Date: November 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   40 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00135551

Locations
Japan
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.
Investigators
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
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Seiji Umemoto, M.D., Ph.D., Associate Professor, COPE Trial Group
ClinicalTrials.gov Identifier: NCT00135551     History of Changes
Other Study ID Numbers: copeadministrator
Study First Received: August 24, 2005
Last Updated: February 19, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by COPE Trial Group:
Hypertension
Multicenter clinical trial
PROBE
Combination therapy
Benidipine
Essential Hypertension

Additional relevant MeSH terms:
Cardiovascular Diseases
Hypertension
Vascular Diseases
Diuretics
Sodium Chloride Symporter Inhibitors
Benidipine
Angiotensin Receptor Antagonists
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium Channel Blockers
Cardiovascular Agents
Therapeutic Uses
Vasodilator Agents

ClinicalTrials.gov processed this record on July 23, 2014