Efficacy of Sevikar® 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.

BACKGROUND AND RATIONALE

To date, few studies have investigated the effects of combined renin-angiotensin system blockade/calcium channel blockade on central aortic blood pressure. The Conduit Artery Function Evaluation (CAFE) sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) investigated the effects of amlodipine/perindopril and atenolol/bendroflumethiazide on central aortic blood pressure (CABP). Similar brachial blood pressure levels were achieved; however, there was a significant difference, in favor of the amlodipine/perindopril combination, on the effects of CABP. No study has investigated the effects of a combination of an angiotensin receptor blocker/calcium channel blocker compared to those of a calcium channel blocker/angiotensin-converting enzyme inhibitor combination. To confirm and support previous findings, the SEVITENSION study will assess the effects on CABP of treatment with the high dose combination of perindopril plus amlodipine as used in ASCOT-CAFE compared with the high dose combination of olmesartan/amlodipine in patients with moderate-to-severe hypertension uncontrolled on amlodipine monotherapy.

OBJECTIVE

To demonstrate non-inferiority of fixed-dose olmesartan/amlodipine combination therapy compared with the combination of perindopril plus amlodipine on the mean change from baseline in central aortic systolic blood pressure.

DESIGN

A multicenter, double-blind, parallel-group, non-inferiority study comprising a 2-4-week open-label run-in period with amlodipine and a 24-week active treatment period. CABP will be measured by the SphygmoCor® Vx Pulse Wave Velocity System.

PATIENTS

720 moderate-to-severe hypertensive patients aged ≥ 40 to ≤ 80 years and ≥ 3 additional risk factors will be enrolled.

INTERVENTIONS

Study treatment will comprise orally-administered combination of olmesartan/amlodipine (40/10mg) or perindopril (8 mg) plus amlodipine (10mg), and matching placebos. (EudraCT number: 2009-012966-30; ClinicalTrials.gov identifier: NCT01101009).