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

Condition(s) targeted: Hypertension

Intervention: Perindopril + amlodipine + if necessary, hydrochlorothiazide (Drug); olmesartan/amlodipine + hydrochlorothiazide, if necessary. (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Daiichi Sankyo Europe, GmbH

Overall contact:
Luis Ruilope, Phone: 91 390 80 00

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.

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 design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: 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.

Secondary outcome:

Changes in systolic and diastolic ambulatory blood pressure (mean of 24h, daytime and night-time)

Changes in conventional mean sitting systolic and diastolic blood pressure measurement

Incidence and profile of AEs separately by Run-in Phase and by double-blind Treatment Phase

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.

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.

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.

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.

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.

Minimum age: 40 Years. Maximum age: 80 Years. Gender(s): Both.

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,

Luis Ruilope, Phone: 91 390 80 00

Albacete 02200, Spain; Recruiting
Juan A Divison, Phone: +34 967 46 07 52
Juan A Divison, Principal Investigator

Barcelona 08003, Spain; Recruiting
Anna Oliveras, Phone: +34 932211010
Anna Oliveras, Principal Investigator

Cadiz 11407, Spain; Recruiting
Pablo Gomez, Phone: +34 956 03 20 00
Pablo Gomez, Principal Investigator

Madrid 28041, Spain; Recruiting
Luis M Ruilope, Phone: +34 91 390 80 00
Luis M Ruilope, Principal Investigator

Madrid, Spain; Recruiting
Luis Vigil, Phone: +34 91 664 86 00
Luis Vigil, Principal Investigator

Madrid 28006, Spain; Recruiting
Carmen Suarez, Phone: +34 91 520 22 00
Carmen Suarez, Principal Investigator

Madrid 28040, Spain; Recruiting
Nieves Martell, Phone: +34 913 30 30 00
Nieves Martell, Principal Investigator

Salamanca, Spain; Recruiting
Luis Garcia, Phone: +34 923126591
Luis Garcia, Principal Investigator

Sevilla 41009, Spain; Recruiting
Josefina Olivan, Phone: +34 955 00 80 00
Josefina Olivan, Principal Investigator

Starting date: April 2010
Last updated: June 16, 2011