Comparison of Sevikar® and the Combination of Perindopril/Amlodipine on Central Blood Pressure

NCT ID: NCT01101009

Last Updated: 2018-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

486 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-04-30

Study Completion Date

2012-12-31

Brief Summary

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Comparison of the combination of amlodipine with an angiotensin receptor blocker or an angiotensin converting inhibitor, on central arterial blood pressure in patients with hypertension and additional risk factors. This is a randomised, double-blind, double-dummy, multicenter study. The duration of active treatment 24 weeks.

Detailed Description

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The study, multi-center balanced, parallel group (two treatment arms), randomized, double-blind (double-dummy), non-inferiority study is designed to show non-inferiority of Sevikar® (olmesartan(OM)/amlodipine (AM)) 40/10 mg compared to the combination of Perindopril (PER) 8 mg plus Amlodipine 10 mg with regard to central systolic blood pressure lowering effect, using the change from baseline (Week 0) to final examination (Week 24).

Male and female Caucasians aged ≥ 40 years and \<80 years with moderate to severe hypertension, defined by a systolic blood pressure (SBP) ≥ 160 and ≤ 200 or diastolic blood pressure (DBP) ≥ 100 and ≤ 115 mmHg for untreated patients, SBP ≥ 140 or DBP ≥ 90 mmHg for insufficiently pre-treated patients and SBP ≥ 130 mmHg or DBP ≥ 80 mmHg for insufficiently pretreated diabetics chronic kidney disease will be eligible for participation. In addition,three additional risk factors should be present.

During the course of the study three central blood pressure measurements (at randomization, at week 12 and at termination) will be performed with SphygmoCor ultrasound method. The conventional measurements with calibrated tensiometers (Omron) will be performed at each visit. Ambulatory blood pressure monitoring will be performed at randomisation.

The study starts with a 2-4 week run in phase. AM will be given as open-labelled 5 mg or 10 mg tablets, administered once daily. After randomization during the double-blind phase, study medication will comprise either OM/AM 40/10 mg or PER 8 mg (2x4 mg) plus AM 10 mg and will be administered once daily. Furthermore, open-label HCTZ 12.5 mg and 25.0 mg will be provided in tablets and administered once daily according to the treatment schedule.

The primary endpoint is the change in central SBP from baseline (Week 0, Visit 0) to final examination (Week 24, Visit 5) using Last Observation Carried Forward (LOCF) approach.

The study is conducted in approximately 15 centres in Spain. Depending on the previously administered drugs the run in phase is up to four weeks (Visits -2 and -1). Individual duration of active treatment (after randomization) will last 24 weeks (Visits 0-5). The total individual duration is 28 weeks.

A total of 518 patients (259 patients/arm) will be needed in the Per Protocol Set (PPS) for the confirmatory primary analysis using mean change from baseline (Week 0) to Final Examination assuming a drop out rate of 20% during Run-in Phase a total of 720 patients have to be screened in order to achieve 576 (288 patients/arm) randomised patients.

Assuming approximately 10% major protocol deviations, a total of 518 patients will remain in the PPS.

Conditions

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Hypertension

Keywords

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Sevikar® Central Arterial Blood Pressure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Perindopril+amlodipine

Group Type ACTIVE_COMPARATOR

Perindopril + amlodipine + if necessary, hydrochlorothiazide

Intervention Type DRUG

Two perindopril 4 mg tablets + 1 amlodipine 10 mg tablet + placebo tablet matching the olmesartan/amlodipine tablet. All tablets are taken once daily. The duration of administration of perindopril tablets and placebo is 24 weeks. The duration of administration of amlodipine tablets is 24-26 weeks. Hydrochlorthiazide tablets 12.5 mg or 25 mg, once daily, will be added, if necessary

Olmesartan/amlodipine

Group Type ACTIVE_COMPARATOR

olmesartan/amlodipine + hydrochlorothiazide, if necessary.

Intervention Type DRUG

olmesartan/amlodipine tablets 40 mg/10 mg, + placebo tablets matching the perindopril tablet and amlodipine tablet. All tablets are taken once daily for 24 weeks. Hydrochlorthiazide tablets 12.5 mg or 25 mg, once daily, will be added, if necessary

Interventions

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Perindopril + amlodipine + if necessary, hydrochlorothiazide

Two perindopril 4 mg tablets + 1 amlodipine 10 mg tablet + placebo tablet matching the olmesartan/amlodipine tablet. All tablets are taken once daily. The duration of administration of perindopril tablets and placebo is 24 weeks. The duration of administration of amlodipine tablets is 24-26 weeks. Hydrochlorthiazide tablets 12.5 mg or 25 mg, once daily, will be added, if necessary

Intervention Type DRUG

olmesartan/amlodipine + hydrochlorothiazide, if necessary.

olmesartan/amlodipine tablets 40 mg/10 mg, + placebo tablets matching the perindopril tablet and amlodipine tablet. All tablets are taken once daily for 24 weeks. Hydrochlorthiazide tablets 12.5 mg or 25 mg, once daily, will be added, if necessary

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* moderate to severe hypertension
* 3 additional risk factors such as age \> 55 (male), \> 65 female, smoker, type 2 diabetes, obesity, cardiovascular disease, congestive heart failure, chronic kidney disease,
* ability to give informed consent

Exclusion Criteria

* secondary or malignant hypertension
* contraindication to any of the study drugs
* Creatinine clearance level \<40ml/min
* treatment with more than 3 antihypertensive drugs
* Myocardial infarction, percutaneous transluminal coronary angioplasty, cardiac bypass surgery \< 6 month prior to start of the study,
* unstable angina pectoris,
* stroke, transient ischemic attack \< 3 months prior to start,
* Congestive heart failure NYHA II-IV,
* clinically relevant concomitant diseases,
* alcohol or drug abuse,
* pregnancy or women of childbearing potential without contraceptive precaution,
Minimum Eligible Age

40 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Centro de Salud Casas Ibañez

Albacete, , Spain

Site Status

Hospital del Mar

Barcelona, , Spain

Site Status

Hospital General de Jerez de la Frontera

Cadiz, , Spain

Site Status

Hospital Universitario de Fuenlabrada

Fuenlabrada (Madrid), , Spain

Site Status

Hospital Universitario La Princesa

Madrid, , Spain

Site Status

Hospital Universitario 12 Octubre

Madrid, , Spain

Site Status

Hospital General Universitario La Paz

Madrid, , Spain

Site Status

Hospital Universitario Clínico San Carlos

Madrid, , Spain

Site Status

Hospital Universitario de Móstoles

Madrid, , Spain

Site Status

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Site Status

Hospital General Carlos Haya

Málaga, , Spain

Site Status

Centro de Salud Murcia San Andrés

Murcia, , Spain

Site Status

Hospital de Sagunto

Puerto de Sagunto (Valencia), , Spain

Site Status

Centro de Salud La Alamedilla

Salamanca, , Spain

Site Status

Hospital Virgen de la Macarena

Seville, , Spain

Site Status

Countries

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Spain

References

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Ruilope L, Schaefer A. The fixed-dose combination of olmesartan/amlodipine was superior in central aortic blood pressure reduction compared with perindopril/amlodipine: a randomized, double-blind trial in patients with hypertension. Adv Ther. 2013 Dec;30(12):1086-99. doi: 10.1007/s12325-013-0076-6. Epub 2013 Nov 30.

Reference Type DERIVED
PMID: 24293132 (View on PubMed)

Ruilope LM, Schaefer A. Efficacy of Sevikar(R) compared to the combination of perindopril plus amlodipine on central arterial blood pressure in patients with moderate-to-severe hypertension: Rationale and design of the SEVITENSION study. Contemp Clin Trials. 2011 Sep;32(5):710-6. doi: 10.1016/j.cct.2011.04.011. Epub 2011 May 14.

Reference Type DERIVED
PMID: 21586342 (View on PubMed)

Other Identifiers

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2009-012966-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DSE- SEV-02-09

Identifier Type: -

Identifier Source: org_study_id