Clinical trial NCT01101009: Comparison of Sevikar® and the Combination of Perindopril/Amlodipine on Central Blood Pressure
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Keywords: Sevikar®
Central Arterial Blood Pressure
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2010-04-09
Enrollment: 486
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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,

Primary outcomes:
measure: 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.
timeFrame: Baseline to week 24
Secondary outcomes:
measure: Changes in systolic and diastolic ambulatory blood pressure (mean of 24h, daytime and night-time)
timeFrame: Baseline to week 24
measure: Changes in conventional mean sitting systolic and diastolic blood pressure measurement
timeFrame: Baseline to 24 weeks
measure: Incidence and profile of AEs separately by Run-in Phase and by double-blind Treatment Phase
timeFrame: Run in phase (2 weeks) to end of study (24 weeks)
measure: 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.
timeFrame: Baseline to 24 weeks
measure: 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.
timeFrame: Baseline to 24 weeks
measure: 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.
timeFrame: Week 12 to Week 18 or week 24
measure: 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.
timeFrame: Week 12 to week 18 or week 24
Other outcomes:
Locations:
city: Albacete
country: Spain
facility: Centro de Salud Casas Ibañez
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Cadiz
country: Spain
facility: Hospital General de Jerez de la Frontera
city: Fuenlabrada (Madrid)
country: Spain
facility: Hospital Universitario de Fuenlabrada
city: Madrid
country: Spain
facility: Hospital Universitario La Princesa
city: Madrid
country: Spain
facility: Hospital Universitario 12 Octubre
city: Madrid
country: Spain
facility: Hospital General Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario de Móstoles
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Malaga
country: Spain
facility: Hospital General Carlos Haya
city: Murcia
country: Spain
facility: Centro de Salud Murcia San Andrés
city: Puerto De Sagunto (Valencia)
country: Spain
facility: Hospital de Sagunto
city: Salamanca
country: Spain
facility: Centro de Salud La Alamedilla
city: Sevilla
country: Spain
facility: Hospital Virgen de la Macarena
Study officials:
References:
citation: 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.
citation: 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.