Open-label inteRventional Clinical Trial to Assess Efficacy and Safety of the exteMporaneous combInation of Nebivolol and Ramipril in hypertenSIve pAtients

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 thestudy and provided signed, written informed consent prior to any study procedures atScreening Visit.

2. Male or female patients aged ≥ 18 years 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) and, as per Investigator'sjudgement, is deemed appropriate for a combination treatment with BB and ACE-i.

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 notpregnant, or not breastfeeding. A woman is considered fertile following menarche anduntil becoming postmenopausal unless permanently sterile. Women of childbearingpotential must agree to use of highly effective contraception (e.g., method of birthcontrol throughout the study period and for 4 weeks after study completion definedas a method which results in a failure rate of less than 1% per year) and also mustrefrain from donating or storing eggs during this time. Highly effectivecontraception 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 thescreening), (provided that partner is the sole sexual partner of the trialparticipant and that the vasectomized partner has received medical assessmentof the surgical success).

5. A male patient must agree to use contraception during the whole study period and forat least 1 week after the last dose of study treatment and refrain from donatingsperm during this period.

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 otherACE-is, or any related products, excipients of the formulations, as outlined in therelevant Investigator's Brochure (IB), summary of product characteristics (SmPC) orlocal package inserts for Nebivolol and Ramipril.

2. Patients with serious disorders (in the opinion of the Investigator) which may limitthe ability to evaluate the efficacy or safety of the tested medications, includingcerebrovascular, cardiovascular, renal, respiratory, hepatic, gastrointestinal,endocrine, or metabolic, hematological, or oncological, neurological, andpsychiatric diseases. The same applies for immunocompromised and/or neutropenicpatients.

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 ofheart 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.

7. Patients with severe heart failure (New York Heart Association classificationIII-IV) a narrowing of the aortic or bicuspid valve, an obstruction of cardiacoutflow (obstructive, hypertrophic cardiomyopathy), obstruction of the outflow tractof the left ventricle (e.g., high grade aortic stenosis) or symptomatic coronarydisease.

8. Patients with clinical evidence of renal disease (including significant bilateralrenal artery stenosis or renal artery stenosis in a single functioning kidney),severe renal impairment or renal transplant.

9. Patients with clinically relevant hepatic impairment.

10. Patients with a history of angioneurotic edema.

11. Patients with sick sinus syndrome, including sino-atrial block.

12. Patient with second- and third-degree heart block (without a pacemaker).

13. History of bronchospasm and bronchial asthma.

14. Untreated phaeochromocytoma.

15. Patients with bradycardia (heart rate < 60 bpm; < 50 bpm in patients already on BBstreatment).

16. Patient with history of metabolic acidosis.

17. Patients with severe peripheral circulatory disturbances.

18. Participation in another interventional study within the last 30 days beforeScreening Visit (Visit 1).

19. Patients with diseases that, in the opinion of the Investigator, prevent a carefuladherence to the protocol.

20. Patients using and not suitable for withdrawing the prohibited medications prior tothe administration of study treatment.

21. Pregnant and breastfeeding women. NOTE: a pregnancy test will be performed on allwomen of childbearing potential at each study visit.

22. Patients with medical history of cirrhosis (Child Pugh class B or higher).

23. History of unexplained syncope within the prior 2 years, or a known syncopaldisorder.

24. Patients who received renal denervation in the last 3 years or other device-basednonpharmacological treatment of hypertension.

25. Any other contraindication to either NEB or RAM as per respective SmPC.