Clinical trial NCT00135551: Benidipine-based Comparison of Angiotensin Receptors, β-blockers, or Thiazide Diuretics in Hypertensive Patients
Official title: The Combination Therapy of Hypertension to Prevent Cardiovascular Events Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cardiovascular Disease
Keywords: Hypertension
Multicenter clinical trial
PROBE
Combination therapy
Benidipine
Essential Hypertension
Lead sponsor: COPE Trial Group
Sponsor class: OTHER
Collaborators: name: The Japanese Society of Hypertension
name: Yamaguchi University Hospital
name: Kyowa Hakko Kogyo Co., Ltd.
First posted: 2005-08-26
Enrollment: 3501
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility 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

Primary outcomes:
measure: A composite of fatal and non-fatal cardiovascular events.
timeFrame: first event
measure: Achievement of target blood pressure (< 140 mmHg/90 mmHg).
timeFrame: time course
Secondary outcomes:
measure: All-cause mortality.
timeFrame: first event
measure: Death from cardiovascular events.
timeFrame: first event
measure: Fatal and non-fatal cardiovascular events.
timeFrame: first event
measure: Hospitalization due to heart failure.
timeFrame: first event
measure: New onset of diabetes mellitus.
timeFrame: first event
measure: Safety (adverse events and adverse drug reaction).
timeFrame: total number
Other outcomes:
Locations:
city: Ube
country: Japan
facility: Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine
state: Yamaguchi
Study officials:
affiliation: Department of Geriatric Medicine, Osaka University Graduate School of Medicine
name: Toshio Ogihara, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Internal Medicine, Keio University School of Medicine
name: Takao Saruta, MD, PhD
role: STUDY_CHAIR
References:
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. doi: 10.1291/hypres.28.331.
citation: 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.
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 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.
citation: 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.
citation: 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.
citation: 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.