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CompletedNCT00135551COPEUpdated Feb 22, 2012

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

A Phase 4 interventional study of Angiotensin receptor blockers and β-blockers in Cardiovascular Disease, sponsored by Seiji Umemoto, M.D., Ph.D.. Completed at 1 site in Japan. Open to participants aged 40 Years to 85 Years. Per ClinicalTrials.gov, last updated 2012-02-22.

Sponsored by Seiji Umemoto, M.D., Ph.D. · Phase 4, Interventional, and Prevention

Phase
Phase 4
Study type
Interventional
Enrollment
3,501
Allocation
Randomized
Ages
40 Years to 85 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Cardiovascular Disease

Keywords

  • Hypertension
  • Multicenter clinical trial
  • PROBE
  • Combination therapy
  • Benidipine
  • Essential Hypertension
03

In context

Cardiovascular Diseases

5,025 studies on the registry are indexed under Cardiovascular Diseases; 930 are open to participants now.

This study's enrollment of 3,501 is above the median of 100 across 2,801 interventional studies indexed under Cardiovascular Diseases.

Browse Cardiovascular Diseases studies →

Lead sponsor

This is the only study on the registry with Seiji Umemoto, M.D., Ph.D. as lead sponsor.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
40 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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
05

Study design

Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
3,501 participants (actual)

Study arms

  • Active comparator
    angiotensin receptor blockers

    benidipine+angiotensin receptor blockers, titlation scheme

    Drug: Angiotensin receptor blockers

  • Active comparator
    β-blockers

    benidipie+β-blockers, titlation scheme

    Drug: β-blockers

  • Active comparator
    thiazide diuretics

    benidipine+thiazide diuretics, titlation scheme

    Drug: thiazide diuretics

Interventions

  • DrugAngiotensin receptor blockers

    benidipine+angiotensin receptor blocker, titlation scheme

    Also known as: benidipine, angiotensin receptor blockers

  • Drugβ-blockers

    benidipine+β-blockers, titlation scheme

    Also known as: benidipine, β-blockers

  • Drugthiazide diuretics

    benidipie+thiazide diuretics, titlation scheme

    Also known as: benidipie, thiazide diuretics

06

What researchers measure

Primary outcomes

  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 outcomes

  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

07

Study locations

1 site
  • Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine
    Ube, Yamaguchi 755-8505, Japan
08

References and documents

Publications

  • 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. PubMed 16138563 ↗
  • 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. PubMed 21610513 ↗
  • 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. PubMed 22278623 ↗
  • 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. PubMed 31995012 ↗
  • 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. PubMed 26490089 ↗
  • 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. PubMed 23985703 ↗
09

Timeline

Tracking since Sep 25, 2026
Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of May 2003, a primary completion of May 2010 and a completion of Nov 2010. It does not say whether these dates are actual or estimated.

How these figures are worked out, and which studies are left out of them.

Registered
Aug 24, 2005
First posted
Aug 26, 2005
Start
May 2003
Primary completionActual
May 2010
CompletionActual
Nov 2010
Last update
Feb 22, 2012
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Feb 22, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00135551
Lead sponsor
Seiji Umemoto, M.D., Ph.D.
Collaborators
The Japanese Society of Hypertension, Yamaguchi University Hospital, Kyowa Hakko Kogyo Co., Ltd.
Responsible party
Seiji Umemoto, M.D., Ph.D. (Associate Professor, COPE Trial Group) — Sponsor-investigator
First posted
Aug 26, 2005
Start date
May 2003
Primary completion
May 2010
Completion
Nov 2010
Last update
Feb 22, 2012

Study contacts

Toshio Ogihara, MD, PhD
principal investigator · Department of Geriatric Medicine, Osaka University Graduate School of Medicine
Takao Saruta, MD, PhD
study chair · Department of Internal Medicine, Keio University School of Medicine

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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