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

NCT06104423 | Completed Phase 4 Results

• 2 other identifiers: MEIN/22/NeRam-Hyp/0012022-003060-25
• Study Type: interventional
• Target: 266
• Locations: 1 country
• Sites: 1

Brief Summary

Open-label, inteRventional clinical Trial to assess EffIcacy and safety of the exteMporaneous combInation of Nebivolol and Ramipril in hypertenSIve pAtients.

Conditions

Hypertension

Keywords

Hypertension; Combination Therapy; Nebivolol; Ramipril; Fixed Dose Combination

Outcome Measures

Primary Outcomes (1)

• Primary Outcome: Change in Mean Sitting SBP

  To assess the antihypertensive efficacy of the extemporaneous combination of Nebivolol 5 mg in combination with Ramipril 2.5 mg or 5 mg or 10 mg in lowering the sitting systolic BP between Visit 2(Week 0) and Visit 5 (Week 12) in patients with uncontrolled BP previously treated with Nebivolol 5 mg or Ramipril 5 mg monotherapies for at least 4 weeks during run-in period.

  12 weeks of combination therapy treatment. From study Visit 2 (Week 0) to study Visit 5 (Week 12)

Study Arms (2)

Nebivolol 5 mg

ACTIVE COMPARATOR

MONOTHERAPY PERIOD 1 (4 weeks): Eligible patients entered a 4 weeks run-in period (week -4 to week 0) on the same day of the screening visit. Patients previously receiving Neb 5 mg continued the same treatment, while patients receiving any other BBs were switched to Neb 5 mg. COMBINATION THERAPY PERIOD 2 (12 weeks): During the Assessment period of 12 weeks (week 0\_Baseline to week 12) uncontrolled patients will be treated with the extemporaneous combination of Nebivolol 5 mg and Ramipril 2.5 mg for 4 weeks. Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg in uncontrolled patients for further 4 weeks while controlled patients will continue with Nebivolol 5 mg/Ramipril 2.5 mg therapy. After 8 weeks Ramipril 5 mg will be up-titrated to Ramipril 10 mg in the uncontrolled patients as well as Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg. Controlled patients will continue same therapy.

Drug: Nebivolol 5 mg; Drug: Ramipril 2.5/5/10 mg

Ramipril 2.5/5/10 mg

ACTIVE COMPARATOR

MONOTHERAPY PERIOD 1 (4 weeks): Eligible patients entered a 4 week run-in (week -4 to week 0) period on the same day of the screening visit. Patients previously receiving RAM 5 mg continued the same treatment, while patients receiving any other ACE-i were switched to RAM 5 mg. COMBINATION THERAPY PERIOD 2 (12 weeks): During the Assessment period of 12 weeks (week 0\_Baseline to week 12) uncontrolled patients will be treated with the extemporaneous combination of Nebivolol 5 mg and Ramipril 2.5 mg for 4 weeks. Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg in uncontrolled patients for further 4 weeks while controlled patients will continue with Nebivolol 5 mg/Ramipril 2.5 mg therapy. After 8 weeks Ramipril 5 mg will be up-titrated to Ramipril 10 mg in the uncontrolled patients as well as Ramipril 2.5 mg will be up-titrated to Ramipril 5 mg. Controlled patients will continue same therapy.

Drug: Nebivolol 5 mg; Drug: Ramipril 2.5/5/10 mg

Interventions

Nebivolol 5 mg DRUG

1 tablet of study medication (5mg) to be administered orally according to instructions of Investigator.

Nebivolol 5 mg; Ramipril 2.5/5/10 mg

Ramipril 2.5/5/10 mg DRUG

1 tablet of study medication (2.5mg or 5mg or 10mg) to be administered orally according to instructions of Investigator.

Nebivolol 5 mg; Ramipril 2.5/5/10 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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's judgement, is deemed appropriate for a combination treatment with BB and ACE-i.
• Ability to take oral medication and willing to adhere to the drug regimen.
• 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 of 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).
• A male patient 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.

You may not qualify if:

• Any patient who meets any of the following criteria will not qualify for entry into the study:
• Patients with documented history of hypersensitivity to NEB, RAM, other BBs or other ACE-is, or any related products, excipients of the formulations, as outlined in the relevant Investigator's Brochure (IB), summary of product characteristics (SmPC) or local package inserts for Nebivolol and Ramipril.
• 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.
• 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.
• Patients with condition of hypotension with SBP \< 90 mmHg and/or DBP \< 60 mmHg.
• Acute heart failure (12 months before enrolment), cardiogenic shock, or episodes of heart failure decompensation requiring intravenous inotropic therapy.
• Patients with secondary hypertension of any etiology including renal diseases, Cushing's syndrome, hyperaldosteronism, renovascular disease and thyroid disorders.
• Patients with severe heart failure (New York Heart Association classification III-IV) a narrowing of the aortic or bicuspid valve, an obstruction of cardiac outflow (obstructive, hypertrophic cardiomyopathy), obstruction of the outflow tract of the left ventricle (e.g., high grade aortic stenosis) or symptomatic coronary disease.
• Patients with clinical evidence of renal disease (including significant bilateral renal artery stenosis or renal artery stenosis in a single functioning kidney), severe renal impairment or renal transplant.
• Patients with clinically relevant hepatic impairment.
• Patients with a history of angioneurotic edema.
• Patients with sick sinus syndrome, including sino-atrial block.
• Patient with second- and third-degree heart block (without a pacemaker).
• History of bronchospasm and bronchial asthma.

Sponsors & Collaborators

• Menarini International Operations Luxembourg SA: lead

Study Sites (1)

A & P Kft.

Hosszúhetény, 7694, Hungary

Location

MeSH Terms

Conditions

Hypertension

Interventions

Nebivolol; Ramipril

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Simone Baldini Global Clinical Operations Manager
• Organization: A.MENARINI I.F.R SrL

sbaldini@menarini.it

055 56801

Study Officials

• Giovambattista Desideri, Prof

  University of Roma La Sapienza

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2023
• First Posted: October 27, 2023
• Study Start: October 2, 2023
• Primary Completion: February 19, 2024
• Study Completion: February 19, 2024
• Last Updated: April 24, 2025
• Results First Posted: April 24, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

HU (1)