AzTrials
AzTrials

HypertensionPhase 4ARTEMISIANCT06104423

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

A Phase 4 study testing Nebivolol 5 mg and Ramipril 2.5/5/10 mg in people with Hypertension, run by Menarini International Operations Luxembourg SA at 1 site in Hungary.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Hypertension
What is being tested?
Nebivolol 5 mg and Ramipril 2.5/5/10 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
266 participants
Where
1 siteHungary
Study dates
2 Oct 2023to 19 Feb 2024
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient will be considered eligible to be enrolled in the study only if he/she meets all the following inclusion criteria:
  • 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:
Show all 13Show fewer
  • 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.

Who cannot join

  • 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.
Show all 27Show fewer
  • 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.
  • Untreated phaeochromocytoma.
  • Patients with bradycardia (heart rate < 60 bpm; < 50 bpm in patients already on BBs treatment).
  • Patient with history of metabolic acidosis.
  • Patients with severe peripheral circulatory disturbances.
  • Participation in another interventional study within the last 30 days before Screening Visit (Visit 1).
  • Patients with diseases that, in the opinion of the Investigator, prevent a careful adherence to the protocol.
  • Patients using and not suitable for withdrawing the prohibited medications prior to the administration of study treatment.
  • Pregnant and breastfeeding women. NOTE: a pregnancy test will be performed on all women of childbearing potential at each study visit.
  • Patients with medical history of cirrhosis (Child Pugh class B or higher).
  • History of unexplained syncope within the prior 2 years, or a known syncopal disorder.
  • Patients who received renal denervation in the last 3 years or other device-based nonpharmacological treatment of hypertension.
  • Any other contraindication to either NEB or RAM as per respective SmPC.

Trial locations and contacts

1 site in 1 country.

Hungary1 site
  • A & P Kft.

    Hosszúhetény, 7694

Other trials in Hungary

About this study

Official title: Open-label, Multicenter, multinAtionaL, inteRventional Clinical Trial to Assess Efficacy and Safety of the exteMporaneous combInation of Nebivolol and Ramipril in hypertenSIve pAtients - ARTEMISIA Study

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

Read the detailed description

This is a Phase IV, interventional, multicenter, open-label, multinational study with 2 study periods (a Run-in period of 4 weeks and an Assessment period of 12 weeks) to assess the efficacy and safety of the extemporaneous combination of Nebivolol (NEB) and Ramipril (RAM) in reducing Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) in hypertensive patients uncontrolled by monotherapy.

The trial was conducted in 16 investigational clinical sites in Bulgaria, Poland, and Hungary.

Note: For the purpose of this study, uncontrolled blood pressure (BP) is defined as sitting SBP/DBP:

  • ≥ 130/80 mmHg in patients < 65 years old
  • ≥ 140/80 mmHg in patients ≥ 65 years old

Screening Visit 1 (Week -4):

Hypertensive patients with SBP ranging from ≥ 140 to ≤ 179 mmHg and/or DBP ranging from ≥ 90 to ≤ 109 mmHg on treatment, for at least 30 days prior to screening, with NEB 5 mg or any other Beta Blockers (BBs), or RAM 5 mg or any other Angiotensin-converting enzyme inhibitors (ACE-i) will be screened for eligibility (Visit1). Patients that did not meet eligibility criteria will be considered as screening failures and will not be re-screened.

Run-in period from Visit 1 (Week -4) to Visit 2 (Week 0):

On the same day of the Screening Visit, eligible patients will enter a Run-in period, during which:

  • Patients receiving NEB 5 mg or RAM 5 mg will continue the same therapy for 4 weeks.
  • Patients on any other BB will be assigned to monotherapy with NEB 5 mg while patients on any other ACE-i will be assigned to monotherapy with RAM 5 mg for 4 weeks. The study is designed in order to ensure that 1:1 ratio between patients in the NEB and RAM arms will be achieved.

Assessment period from Visit 2 (Week 0) to Visit 5 (Week 12):

After 4 weeks (± 2 days) of the Run-in period of monotherapy (Week 0), BP will be further assessed at Visit 2. Patients with uncontrolled BP levels (sitting BP ≥ 130/80 mmHg in patients < 65 years old/sitting BP ≥ 140/80 mmHg in patients ≥ 65 years old) at Visit 2, with adequate treatment adherence (ranging between 80% to 120%) and who did tolerate the treatment, will enter into the Assessment period and will be assigned to the extemporaneous combination of NEB/RAM 5/2.5 mg. Patients with controlled BP levels (sitting BP < 130/80 mmHg in patients < 65 years old/sitting BP < 140/80 mmHg in patients ≥ 65 years old) and/or who do not tolerate the treatment or have an adherence range below 80% or above 120%, will be withdrawn from the study (drop-out patients).

After 4 weeks ± 2 days in the Assessment period (Week 4), patients BP will be further evaluated at Visit 3: patients with controlled BP levels (sitting BP < 130/80 mmHg in patients < 65 years old/sitting BP < 140/80 mmHg in patients ≥ 65 years old) will continue the same extemporaneous combination, while patients with uncontrolled BP levels (sitting BP ≥ 130/80 mmHg in patients < 65 years old/sitting BP ≥ 140/80 mmHg in patients ≥ 65 years old) will be up-titrated from NEB/RAM 5/2.5 mg to NEB/RAM 5/5 mg for further 4 weeks ± 2 days.

After further 4 weeks ± 2 days (Week 8) the BP will be assessed again (Visit 4): controlled patients will continue the same extemporaneous combination, while uncontrolled patients:

  • if on NEB/RAM 5/2.5 mg, will be up-titrated to NEB/RAM 5/5 mg for further 4 weeks ± 2 days (Visit 5, Week 12);
  • if on NEB/RAM 5/5 mg, will be up-titrated to NEB/RAM 5/10 mg for further 4 weeks ± 2 days (Visit 5, Week 12).

At the end of the Assessment period (12 weeks ± 2 days), at Visit 5, the antihypertensive effect of the extemporaneous combination (NEB/RAM 5/2.5 mg, NEB/RAM 5/5 mg or NEB/RAM 5/10 mg) will be evaluated.

To correctly evaluate the additional effect of the combination therapy, the number of patients with uncontrolled BP on NEB or RAM monotherapy needs to be balanced at Visit 2. To maintain a 1:1 ratio during the Assessment period a cap of 110 patients for each treatment arm (i.e., NEB and RAM) will be included at Visit 2 to maintain a balanced number of uncontrolled patients entering the Assessment period for each drug.

The evaluation will be done every 50 patients. If the entrance in the Assessment period for 1 of the 2 tested drugs will deviate more than 5%, a corrective measure will be initiated: according to the enrollment site statistics, 1 or more sites will be informed to enroll a greater number of patients being treated with the least represented drug in the Assessment period.

Conditions
Hypertension
Being tested
Nebivolol 5 mg, Ramipril 2.5/5/10 mg
Keywords
Hypertension, Combination Therapy, Nebivolol, Ramipril, Fixed Dose Combination
Medical subject headings
Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nebivolol 5 mgDrug

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

  • Ramipril 2.5/5/10 mgDrug

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

Study groups in NCT06104423
Study groupRoleWhat they receive
Nebivolol 5 mgActive comparatorMONOTHERAPY 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.
Receives: Drug: Nebivolol 5 mg; Drug: Ramipril 2.5/5/10 mg
Ramipril 2.5/5/10 mgActive comparatorMONOTHERAPY 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.
Receives: Drug: Nebivolol 5 mg; Drug: Ramipril 2.5/5/10 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Oct 2023
  2. Study start2 Oct 2023
  3. Primary completion19 Feb 2024
  4. Study completion19 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
266 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06104423
Sponsor's protocol ID
MEIN/22/NeRam-Hyp/001
Other IDs
2022-003060-25
Acronym
ARTEMISIA
Status last verified
Apr 2025
First submitted
23 Oct 2023
Last updated
24 Apr 2025
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Nebivolol 5 mg and Ramipril 2.5/5/10 mg in people with Hypertension, run by Menarini International Operations Luxembourg SA at 1 site in Hungary.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Hungary. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Primary Outcome: Change in Mean Sitting SBP (time frame: 12 weeks of combination therapy treatment. From study Visit 2 (Week 0) to study Visit 5 (Week 12)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2025.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in