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AzTrials

Cardiovascular DiseasePhase 4COPENCT00135551

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

A Phase 4 study testing Angiotensin receptor blockers, β-blockers and thiazide diuretics in people with Cardiovascular Disease, run by Seiji Umemoto, M.D., Ph.D. at 1 site in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 40 to 85 years
Conditions the study is for
Cardiovascular Disease
What is being tested?
Angiotensin receptor blockers, β-blockers and thiazide diuretics
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3,501 participants
Where
1 siteJapan
Study dates
May 2003to Nov 2010
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 15Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Japan1 site

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

    Ube, Yamaguchi, 755-8505

Other trials in Japan

About this study

Official title: The Combination Therapy of Hypertension to Prevent Cardiovascular Events Trial

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.

Being tested
Angiotensin receptor blockers, β-blockers, thiazide diuretics
Keywords
Hypertension, Multicenter clinical trial, PROBE, Combination therapy, Benidipine, Essential Hypertension
Medical subject headings
Cardiovascular Diseases, Hypertension, Essential Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Angiotensin receptor blockersDrug

    Also called benidipine, angiotensin receptor blockers

    benidipine+angiotensin receptor blocker, titlation scheme

  • β-blockersDrug

    Also called benidipine, β-blockers

    benidipine+β-blockers, titlation scheme

  • thiazide diureticsDrug

    Also called benidipie, thiazide diuretics

    benidipie+thiazide diuretics, titlation scheme

Study groups in NCT00135551
Study groupRoleWhat they receive
angiotensin receptor blockersActive comparatorbenidipine+angiotensin receptor blockers, titlation scheme
Receives: Drug: Angiotensin receptor blockers
β-blockersActive comparatorbenidipie+β-blockers, titlation scheme
Receives: Drug: β-blockers
thiazide diureticsActive comparatorbenidipine+thiazide diuretics, titlation scheme
Receives: Drug: thiazide diuretics

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: first event

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

    Measured: time course

Secondary outcomes (6)

  1. All-cause mortality.

    Measured: first event

  2. Death from cardiovascular events.

    Measured: first event

  3. Fatal and non-fatal cardiovascular events.

    Measured: first event

  4. Hospitalization due to heart failure.

    Measured: first event

  5. New onset of diabetes mellitus.

    Measured: first event

  6. Safety (adverse events and adverse drug reaction).

    Measured: total number

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Aug 2005 (estimated)
  2. Study startMay 2003
  3. Primary completionMay 2010
  4. Study completionNov 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
3,501 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00135551
Sponsor's protocol ID
copeadministrator
Acronym
COPE
Status last verified
Feb 2012
First submitted
24 Aug 2005
Last updated
22 Feb 2012
Results posted
No
Data monitoring committee
Yes

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

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Angiotensin receptor blockers, β-blockers and thiazide diuretics in people with Cardiovascular Disease, run by Seiji Umemoto, M.D., Ph.D. at 1 site in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Feb 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

A composite of fatal and non-fatal cardiovascular events. (time frame: first event). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00135551, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2012.

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