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

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ClinicalTrials.gov Identifier: NCT01101009
Recruitment Status : Completed
First Posted : April 9, 2010
Last Update Posted : December 24, 2018
Sponsor:
Information provided by (Responsible Party):
Daiichi Sankyo, Inc. ( Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company )

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hypertension Drug: Perindopril + amlodipine + if necessary, hydrochlorothiazide Drug: olmesartan/amlodipine + hydrochlorothiazide, if necessary. Phase 4

Detailed Description:

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 486 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Efficacy of Sevikar® Compared to the Combination of Perindopril/ Amlodipine on Central Arterial Blood Pressure in Patients With Moderate to Severe Hypertension-
Study Start Date : April 2010
Actual Primary Completion Date : November 2012
Actual Study Completion Date : December 2012


Arm Intervention/treatment
Active Comparator: Perindopril+amlodipine Drug: 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

Active Comparator: Olmesartan/amlodipine 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




Primary Outcome Measures :
  1. Change in central systolic blood pressure from baseline (Week 0, Visit 0) to Final Examination (Week 24, Visit 5) using last observation carried forward approach. [ Time Frame: Baseline to week 24 ]

Secondary Outcome Measures :
  1. Changes in systolic and diastolic ambulatory blood pressure (mean of 24h, daytime and night-time) [ Time Frame: Baseline to week 24 ]
  2. Changes in conventional mean sitting systolic and diastolic blood pressure measurement [ Time Frame: Baseline to 24 weeks ]
  3. Incidence and profile of AEs separately by Run-in Phase and by double-blind Treatment Phase [ Time Frame: Run in phase (2 weeks) to end of study (24 weeks) ]
  4. Number of responders at Final Examination defined as normalized or a decrease of systolic blood pressure by at least 20 mmHg or diastolic blood pressure by at least 10 mmHg in conventional BP measurements. [ Time Frame: Baseline to 24 weeks ]
  5. Number of normalized at Final Examination (defined as blood pressure <140/90 mmHg or <130/80 mmHg in diabetics/chronic kidney disease, in conventional BP measurements. [ Time Frame: Baseline to 24 weeks ]
  6. Changes in mean sitting systolic and diastolic blood pressure (BP) measurements from week 12 to Final Exam in patients with stabilized BP (BP is < 140/90 mmHg or < 130/80 mmHg for diabetics/chronic kidney disease) from Week 12 and Week 18. [ Time Frame: Week 12 to Week 18 or week 24 ]
  7. Changes in Central Systolic Blood Pressure from week 12 to Final Examination in patients with stabilised BP (i.e. patients whose BP is < 140/90 mmHg or < 130/80 mmHg for diabetics/chronic kidney disease) between Week 12 and Week 18. [ Time Frame: Week 12 to week 18 or week 24 ]


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Ages Eligible for Study:   40 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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,

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01101009


Locations
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Spain
Centro de Salud Casas Ibañez
Albacete, Spain, 02200
Hospital del Mar
Barcelona, Spain, 08003
Hospital General de Jerez de la Frontera
Cadiz, Spain, 11407
Hospital Universitario de Fuenlabrada
Fuenlabrada (Madrid), Spain
Hospital Universitario La Princesa
Madrid, Spain, 28006
Hospital Universitario 12 Octubre
Madrid, Spain, 28041
Hospital General Universitario La Paz
Madrid, Spain
Hospital Universitario Clínico San Carlos
Madrid, Spain
Hospital Universitario de Móstoles
Madrid, Spain
Hospital Universitario Ramón y Cajal
Madrid, Spain
Hospital General Carlos Haya
Malaga, Spain
Centro de Salud Murcia San Andrés
Murcia, Spain
Hospital de Sagunto
Puerto De Sagunto (Valencia), Spain
Centro de Salud La Alamedilla
Salamanca, Spain
Hospital Virgen de la Macarena
Sevilla, Spain, 41009
Sponsors and Collaborators
Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company
ClinicalTrials.gov Identifier: NCT01101009     History of Changes
Other Study ID Numbers: DSE- SEV-02-09
2009-012966-30 ( EudraCT Number )
First Posted: April 9, 2010    Key Record Dates
Last Update Posted: December 24, 2018
Last Verified: January 2013
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/

Keywords provided by Daiichi Sankyo, Inc. ( Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company ):
Sevikar®
Central Arterial Blood Pressure

Additional relevant MeSH terms:
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Hypertension
Vascular Diseases
Cardiovascular Diseases
Amlodipine
Hydrochlorothiazide
Olmesartan
Olmesartan Medoxomil
Perindopril
Antihypertensive Agents
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Vasodilator Agents
Diuretics
Natriuretic Agents
Sodium Chloride Symporter Inhibitors
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors