Cardiovascular Disease Hypertensive patients MedDRA version: 20.0 Level: PT Classification code 10020772 Term: Hypertension System Organ Class: 10047065 - Vascular disorders
Conditions
Sponsors
Menarini International Operations Luxembourg SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patient will be considered eligible to be enrolled in the study only if he/she meets all the following inclusion criteria: 1. Willing to comply with all study activities and procedures for the duration of the study and provided signed, written informed consent prior to any study procedures at Screening Visit. 2. Male or female patients =18, with hypertension with mean sitting SBP =140 mmHg and =179 mmHg and/or mean sitting DBP =90 mmHg and =109 mmHg at Visit 1 (screening) while on monotherapy treatment either with BBs (NEB 5 mg or any dose if other BB) or ACE-is (RAM 5 mg or any dose if other ACE-i) for at least 30 days before Visit 1 (screening). 3. Ability to take oral medication and willing to adhere to the drug regimen. 4. Female patient of childbearing potential is eligible to participate if she is not pregnant, or not breastfeeding. A woman is considered fertile following menarche and until becoming postmenopausal unless permanently sterile. Women of childbearing potential must agree to use highly effective contraception (e.g., method of birth control throughout the study period and for 4 weeks after study completion defined as a method which results in a failure rate of less than 1% per year) and also must refrain from donating or storing eggs during this time. Highly effective contraception methods can be: • Combined hormonal contraception (estrogen- and progestogen-containing) associated with inhibition of ovulation (oral, intravaginal, and transdermal). • Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, and implantable). • Intrauterine device. • Intrauterine hormone-releasing system. • Bilateral tubal occlusion. • Vasectomized partner (procedure conducted at least 2 months before the screening), (provided that partner is the sole sexual partner of the trial participant and that the vasectomized partner has received medical assessment of the surgical success). 5. A male patient with female sexual partners must agree to use contraception during the whole study period and for at least 1 week after the last dose of study treatment and refrain from donating sperm during this period. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 180 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 90
Exclusion criteria
Exclusion criteria: Any patient who meets any of the following criteria will not qualify for entry into the study: 1. Patients with documented history of hypersensitivity to NEB, RAM, other BBs or other ACE-is, or any related products (including excipients of the formulations) as outlined in the relevant Investigators Brochures, summary of product characteristics or local package inserts for Nebivolol and Ramipril. 2. Patients with serious disorders (in the opinion of the Investigator) which may limit the ability to evaluate the efficacy or safety of the tested medications, including cerebrovascular, cardiovascular, renal, respiratory, hepatic, gastrointestinal, endocrine, or metabolic, hematological, or oncological, neurological, and psychiatric diseases. The same applies for immunocompromised and/or neutropenic patients. 3. Patients having a history of the following conditions within the last 6 months: myocardial infarction, unstable angina pectoris, percutaneous coronary intervention, bypass surgery, heart failure, hypertensive encephalopathy, valve replacement (transcatheter aortic valve implantation, mitraclip), cerebrovascular accident (stroke), or transient ischemic attack. 4. Patients with condition of hypotension with SBP <90 mmHg and/or DBP <60 mmHg. 5. Acute heart failure (12 months before enrolment), cardiogenic shock, or episodes of heart failure decompensation requiring intravenous inotropic therapy. 6. Patients with secondary hypertension of any etiology including renal diseases, Cushing’s syndrome, hyperaldosteronism, renovascular disease and thyroid disorders.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints • Change in mean sitting DBP between Visit 2 (Week 0) and Visit 5 (Week 12). • Change in mean sitting DBP and SBP between: o Visit 2 (Week 0) and Visit 3 (Week 4) o Visit 2 (Week 0) and Visit 4 (Week 8) • Number and proportion of patients achieving the standard BP goal (sitting BP<140/90 mmHg) at Visit 5 (Week 12). • Number and proportion of patients achieving the optimal BP goal (sitting BP<130/80 mmHg in patients < 65 years old/sitting BP<140/80 mmHg in patients = 65 years old) at Visit 5 (Week 12). • Adherence to treatment as (% of doses taken/doses to be taken) at Visit 2 (Week 0), at Visit 3 (Week 4), at Visit 4 (Week 8) and at Visit 5 (Week 12). • Safety and tolerability of the monotherapies (NEB 5 mg and RAM 5 mg) and of the extemporaneous combination (NEB/RAM 5/2.5 mg, NEB/RAM 5/5 mg, NEB/RAM 5/10 mg) measured by incidence, intensity (severity), seriousness of adverse events during the study period, (Screening, Run-in period and Assessment period), relationship to the study treatments, clinically significant abnormal change in vital signs, electrocardiogram (ECG), laboratory parameters, and use of concomitant medications at Visit 2 (Week 0), Visit 3 (Week 4), Visit 4 (Week 8), and Visit 5 (Week 12).;Timepoint(s) of evaluation of this end point: measured in • Change in mean sitting DBP between Visit 2 (Week 0) and Visit 5 (Week 12). • Change in mean sitting DBP and SBP between: o Visit 2 (Week 0) and Visit 3 (Week 4) o Visit 2 (Week 0) and Visit 4 (Week 8) • Achieved the standard BP goal (sitting BP<140/90mmHg) at Visit 5(Week 12) • Achieved optimal BP goal (sitting BP<130/80mmHg in patients <65 years old/sitting BP<140/80mmHg in patients =65 years old) at Visit 5(Week 12). •Adherence to treatment estimated as % of dose taken/doses to be taken at Visit 2 (Week 0), at Visit 3 (Week 4), at Visit 4 (Week 8), and at Visit 5 (Week 12). •Safety and tolerability evaluation - at Visit 2 (Week 0), Visit 3 | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the antihypertensive efficacy of the extemporaneous combination of NEB 5 mg with RAM 2.5/5/10 mg in lowering sitting diastolic blood pressure (DBP) between Visit 2 (Week 0) and Visit 5 (Week 12) in patients with uncontrolled blood pressure (BP)* previously treated with NEB 5 mg or RAM 5 mg monotherapies for at least 30 days. .For the purpose of this study, uncontrolled BP is defined as sitting SBP/DBP =130/80 mmHg.;Secondary Objective: To assess the •antihypertensive efficacy of the extemporaneous combination of NEB5 mg with RAM 2.5/5/10 mg in lowering sitting DBP between Visit 2 (Week 0) and Visit 5 (Week 12) in patients with uncontrolled BP * previously treated with NEB5 mg or RAM5 mg monotherapies for at least 30 days. •antihypertensive efficacy of the extemporaneous combination of NEB5 mg with RAM 2.5/5/10 mg, in lowering sitting DBP and SBP between: - Visit 2(Week 0) and Visit 3(Week 4) - Visit 2(Week 0) and Visit 4(Week 8) •antihypertensive efficacy of the extemporaneous combination of NEB5 mg with RAM 2.5/5/10 mg by evaluating the patients who achieved the standard BP goal (sitting BP <140/90 mmHg) at Visit 5(Week 12). •antihypertensive efficacy of the extemporaneous combination of NEB 5 mg with RAM 2.5/5/10 mg by evaluating the patients who achieved the optimal BP goal (sitting BP <130/80 mmHg in patients <65years old/sitting BP<140/80 mmHg in patients =65 years old) at Visit 5 (Week 12). ;Primary end point(s): The primary endpoint is the change in mean sitting SBP between Visit 2 (Week 0) and Visit 5 (Week 12). The statistical hypothesis will be defined as below: H0: There is no change or increase in the sitting SBP post combination therapy . H1: There is a difference in the sitting SBP post combination therapy. The above hypothesis will be tested as following: • Change from baseline in sitting DBP from prior and post combination therapy will be tested using paired t-test with one-sided significance level of 0.05%. | — |
Countries
Bulgaria, Hungary
Contacts
Public ContactGlobal Clinical Operations Manager
A. MENARINI I.F.R SrL
Outcome results
None listed