Comparison of Sevikar® and the Combination of Perindopril/Amlodipine on Central Blood Pressure
Condition: Hypertension
MeSH terms: Hypertension
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Perindopril + amlodipine + if necessary, hydrochlorothiazide; olmesartan/amlodipine + hydrochlorothiazide, if necessary.
Intervention type(s): Drug; Drug
Intervention description(s): 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 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 MeSH terms: Amlodipine; Hydrochlorothiazide; Olmesartan; Perindopril
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Sevikar®; Central Arterial Blood Pressure