HypertensionPhase 4MasaccioNCT05257148
Effectiveness and Safety of Combination of Nebivolol and Zofenopril in Hypertensive patIents Versus Each Monotherapy
A Phase 4 study testing Zofenopril 30 mg, Nebivolol 5 mg and Zofenopril 30 mg + Nebivolol 5 mg in people with Hypertension, run by Menarini International Operations Luxembourg SA at 1 site in Italy.
Trial summary
Open-label, interventional clinical trial to assess effectiveness and safety of the extemporaneous combination of nebivolol and zofenopril calcium in grade 1 to 2 hypertensive patients versus each monotherapy Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hypertension
- What is being tested?
- Zofenopril 30 mg, Nebivolol 5 mg and Zofenopril 30 mg + Nebivolol 5 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 283 participants
- Where
- 1 siteItaly
- Study dates
- 26 May 2021to 22 Dec 2021
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female Caucasian uncontrolled hypertensive patients (see definition in criterion 3) ≥18 and <65 years of age, in monotherapy either with ACE-i or BBs since at least 1 month, at Screening (Visit 1)
- Patients are able to understand and have freely given written informed consent at Screening
- Patients with mean sitting Systolic Blood Pressure ≥140 mmHg and ≤179 mmHg and/or mean sitting Diastolic Blood Pressure ≥ 90 mmHg and ≤109 mmHg at Screening (Visit 1)
- Patient who are able to comply with all study procedures and who are available for the duration of the study
- Ability to take oral medication and willing to adhere to the drug regimen
- A 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 (eg, 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: a Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal) b Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) c Intrauterine device (IUD) d Intrauterine hormone-releasing system (IUS) e Bilateral tubal occlusion f Vasectomized partner (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 with female partner 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 sperms during this period.
Who cannot join
- Known contraindications, allergies, or hypersensitivities to any of the study medications or excipient as outlined in the investigators brochures (IBs), summary of product characteristics (SmPCs) or local package inserts for NEB and ZOF
- 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 within the last 6 months:
- myocardial infarction, unstable angina pectoris, percutaneous coronary intervention, bypass surgery, heart failure, hypertensive encephalopathy, cerebrovascular accident (stroke), or transient ischemic attack
- Patients with secondary hypertension of any etiology such as renal diseases, pheochromocytoma, or Cushing's syndrome
- 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) or symptomatic coronary disease
Show all 18Show fewer
- Patients with clinical evidence of renal disease as per the Investigator's judgement (including renovascular occlusive disease, nephrectomy and/or renal transplant, bilateral renal artery stenosis or unilateral renal artery stenosis in a solitary kidney, or severe renal impairment)
- History of angioneurotic edema
- Patients with clinically relevant hepatic impairment
- Patients with sick sinus syndrome, including sino-atrial block
- Patients with second- or third-degree heart block (without a pacemaker)
- History of bronchospasm and bronchial asthma
- Patients with bradycardia (heart rate <60 bpm)
- Patient with metabolic acidosis
- Patients with severe peripheral circulatory disturbances
- Participation in another study within the last 4 weeks
- Patients with diseases that, in the opinion of the Investigator, prevent a careful adherence to the protocol
- Pregnant and breastfeeding women. A pregnancy test will be performed on all women of childbearing potential at each study visit
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Open-label, Multicenter, Multinational, Interventional Clinical Trial to Assess Effectiveness and SAfety of the Extemporaneous Combination of Nebivolol and Zofenopril Calcium in Grade 1 to 2 Hypertensive patIents Versus Each mOnotherapy
Open-label, interventional clinical trial to assess effectiveness and safety of the extemporaneous combination of nebivolol and zofenopril calcium in grade 1 to 2 hypertensive patients versus each monotherapy
Read the detailed description
This is a study with 2 periods (a run-in period of 4 weeks and an assessment period of 8 weeks). Grade 1-2 hypertensive patients (blood pressure [BP] ranging from ≥140/90 mmHg to ≤179/109 mmHg) on treatment with any angiotensin converting enzyme-inhibitors (ACEi) or beta blockers (BBs) including ZOF 30 mg or NEB 5 mg respectively will be screened for eligibility (Visit 1).
On the same day, the eligible patients will enter into a run-in period after Screening, during which:
- Patients on ZOF 30 mg or NEB 5 mg will continue the same therapy for 4 weeks
- Patients on any other ACE-i will be assigned to monotherapy with ZOF 30 mg while patients on any other BB will be assigned to monotherapy with NEB 5 mg, respectively, for 4 weeks.
After the 4 weeks of monotherapy in the run-in period, if BP at Visit 2, remains uncontrolled (sitting Systolic Blood Pressure/Diastolic Blood Pressure >130/80 mmHg) despite an adherence to the treatments ranging from 80% to 120%, the patients will start treatment (Week 0, Visit 2) with the extemporaneous combination of NEB 5 mg/ZOF 30 mg (NEB/ZOF) and will be assessed for further 8 weeks (assessment period).
If the patients, at Visit 2 after the Run-In period, have controlled BP (sitting Systolic Blood Pressure/Diastolic Blood Pressure ≤130/80 mmHg), and/or do not tolerate the treatment, and/or do not maintain the adherence to the therapy (range from 80% to 120%), these patients will not be continued further in the study.
At the end of the assessment period (Visit 3) the anti-hypertensive effect of the extemporaneous combination of NEB 5 mg and ZOF 30 mg will be evaluated.
A total number of 290 patients will be screened considering 25% of drop-out rate, to obtain approximately 216 completed patients at the end of the study.
- Conditions
- Hypertension
- Being tested
- Zofenopril 30 mg, Nebivolol 5 mg, Zofenopril 30 mg + Nebivolol 5 mg
- Keywords
- Hypertension, Combination Therapy, Zofenopril, Nebivolol, 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.
Zofenopril 30 mgDrug
Film-Coated tablets administered as one single dose to be taken in the morning (from 6 am to 10 am) with no restriction on food intake
Nebivolol 5 mgDrug
Tablet administered as one single dose to be taken in the morning (from 6 am to 10 am) with no restriction on food intake
Zofenopril 30 mg + Nebivolol 5 mgDrug
Both Film coated tablets of Zofenopril 30 mg and Nebivolol 5 mg Tablets will be taken in the morning (from 6 am to 10 am) with no restriction on food intake
| Study group | Role | What they receive |
|---|---|---|
| Zofenopril arm | Active comparator | MONOTHERAPY PERIOD (one month): patients will be treated with Zofenopril 30 mg. COMBINATION THERAPY PERIOD (two months) patients will be treated with the extemporaneous combination of Zofenopril 30 mg and Nebivolol 5mg Receives: Drug: Zofenopril 30 mg; Drug: Zofenopril 30 mg + Nebivolol 5 mg |
| Nebivolol arm | Active comparator | MONOTHERAPY PERIOD (one month): patients will be treated with Nebivolol 5 mg. COMBINATION THERAPY PERIOD (two months) patients will be treated with the extemporaneous combination of Zofenopril 30 mg and Nebivolol 5 mg Receives: Drug: Nebivolol 5 mg; Drug: Zofenopril 30 mg + Nebivolol 5 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Mean Sitting DBP Between Week 0 (Visit 2) and Week 8 (Visit 3)
To assess the antihypertensive efficacy of the extemporaneous combination of Nebivolol (NEB) 5 mg and Zofenopril (ZOF) 30 mg in lowering sitting diastolic blood pressure (DBP) from baseline (Visit 2) after 8 weeks of treatment (Visit 3), in patients with uncontrolled blood pressure (BP) who were previously treated with NEB or ZOF monotherapies for at least 4 weeks.
Measured: From Baseline (Week 0 - Visit 2) to week 8 (Visit 3)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2022
- Study start26 May 2021
- Primary completion22 Dec 2021
- Study completion22 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Parallel groups
- Model description
- Open Label, two period study. Patients eligible from screening will enter the run-in period on the same day. Patients previously receiving Zofenopril or any other ACE-inhibitor will enter into the run-in period with Zofenopril monotherapy while patients receiving Nebivolol or any other Beta Blockers will enter into the Run-in period with Nebivolol monotherapy in a 1:1 ratio. Only patients with uncontrolled BP (sitting Systolic Blood Pressure/Diastolic Blood Pressure\>130/80 mmHg) and whose adherence to the treatment ranges from 80% to 120%, will enter the assessment period to receive the extemporaneous combination of NEB and ZOF; while the patients with controlled sitting BP (Systolic Blood Pressure/Diastolic Blood Pressure ≤130/80 mmHg) and/or the patients who do not tolerate the treatment and patients with uncontrolled BP whose adherence to the therapy do not range from 80% to 120%, will be withdrawn from the study.
- Masking
- None (open label)
- Enrolment
- 283 participants (actual)
Sponsor and investigators
- Lead sponsor
- Menarini International Operations Luxembourg SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Massimo Volpe, Professor, Principal investigator, University "Sapienza" Rome
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05257148
- Sponsor's protocol ID
- MEIN/19/ZoNe-HYP/001
- Other IDs
- 2020-002340-23
- Acronym
- Masaccio
- Status last verified
- Nov 2023
- First submitted
- 16 Feb 2022
- Last updated
- 20 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Multicenter, Multinational, Interventional Clinical Trial to Assess Effectiveness and SAfety of the Extemporaneous Combination of Nebivolol and Zofenopril Calcium in Grade 1 to 2 Hypertensive patIents Versus Each mOnotherapy
- ClinicalTrials.gov ID
- NCT05257148
- Acronym / sponsor ID
- Masaccio / MEIN/19/ZoNe-HYP/001
- Conditions
- Hypertension
- Keywords
- Hypertension, Combination Therapy, Zofenopril, Nebivolol, Fixed Dose Combination
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 283 participants (actual)
- Lead sponsor
- Menarini International Operations Luxembourg SAIndustry (pharma, biotech, devices)
- Study start
- 26 May 2021 (actual)
- Primary completion
- 22 Dec 2021 (actual)
- Study completion
- 22 Dec 2021 (actual)
- First posted
- 25 Feb 2022 (actual)
- Results
- Posted 20 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Open-label, interventional clinical trial to assess effectiveness and safety of the extemporaneous combination of nebivolol and zofenopril calcium in grade 1 to 2 hypertensive patients versus each monotherapy
Detailed description
This is a study with 2 periods (a run-in period of 4 weeks and an assessment period of 8 weeks). Grade 1-2 hypertensive patients (blood pressure [BP] ranging from ≥140/90 mmHg to ≤179/109 mmHg) on treatment with any angiotensin converting enzyme-inhibitors (ACEi) or beta blockers (BBs) including ZOF 30 mg or NEB 5 mg respectively will be screened for eligibility (Visit 1).
On the same day, the eligible patients will enter into a run-in period after Screening, during which:
- Patients on ZOF 30 mg or NEB 5 mg will continue the same therapy for 4 weeks
- Patients on any other ACE-i will be assigned to monotherapy with ZOF 30 mg while patients on any other BB will be assigned to monotherapy with NEB 5 mg, respectively, for 4 weeks.
After the 4 weeks of monotherapy in the run-in period, if BP at Visit 2, remains uncontrolled (sitting Systolic Blood Pressure/Diastolic Blood Pressure >130/80 mmHg) despite an adherence to the treatments ranging from 80% to 120%, the patients will start treatment (Week 0, Visit 2) with the extemporaneous combination of NEB 5 mg/ZOF 30 mg (NEB/ZOF) and will be assessed for further 8 weeks (assessment period).
If the patients, at Visit 2 after the Run-In period, have controlled BP (sitting Systolic Blood Pressure/Diastolic Blood Pressure ≤130/80 mmHg), and/or do not tolerate the treatment, and/or do not maintain the adherence to the therapy (range from 80% to 120%), these patients will not be continued further in the study.
At the end of the assessment period (Visit 3) the anti-hypertensive effect of the extemporaneous combination of NEB 5 mg and ZOF 30 mg will be evaluated.
A total number of 290 patients will be screened considering 25% of drop-out rate, to obtain approximately 216 completed patients at the end of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Open Label, two period study. Patients eligible from screening will enter the run-in period on the same day. Patients previously receiving Zofenopril or any other ACE-inhibitor will enter into the run-in period with Zofenopril monotherapy while patients receiving Nebivolol or any other Beta Blockers will enter into the Run-in period with Nebivolol monotherapy in a 1:1 ratio. Only patients with uncontrolled BP (sitting Systolic Blood Pressure/Diastolic Blood Pressure>130/80 mmHg) and whose adherence to the treatment ranges from 80% to 120%, will enter the assessment period to receive the extemporaneous combination of NEB and ZOF; while the patients with controlled sitting BP (Systolic Blood Pressure/Diastolic Blood Pressure ≤130/80 mmHg) and/or the patients who do not tolerate the treatment and patients with uncontrolled BP whose adherence to the therapy do not range from 80% to 120%, will be withdrawn from the study.
| Arm | Type | Receives |
|---|---|---|
| Zofenopril arm | Active comparator | Drug: Zofenopril 30 mg, Drug: Zofenopril 30 mg + Nebivolol 5 mgMONOTHERAPY PERIOD (one month): patients will be treated with Zofenopril 30 mg. COMBINATION THERAPY PERIOD (two months) patients will be treated with the extemporaneous combination of Zofenopril 30 mg and Nebivolol 5mg |
| Nebivolol arm | Active comparator | Drug: Nebivolol 5 mg, Drug: Zofenopril 30 mg + Nebivolol 5 mgMONOTHERAPY PERIOD (one month): patients will be treated with Nebivolol 5 mg. COMBINATION THERAPY PERIOD (two months) patients will be treated with the extemporaneous combination of Zofenopril 30 mg and Nebivolol 5 mg |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female Caucasian uncontrolled hypertensive patients (see definition in criterion 3) ≥18 and <65 years of age, in monotherapy either with ACE-i or BBs since at least 1 month, at Screening (Visit 1)
- Patients are able to understand and have freely given written informed consent at Screening
- Patients with mean sitting Systolic Blood Pressure ≥140 mmHg and ≤179 mmHg and/or mean sitting Diastolic Blood Pressure ≥ 90 mmHg and ≤109 mmHg at Screening (Visit 1)
- Patient who are able to comply with all study procedures and who are available for the duration of the study
- Ability to take oral medication and willing to adhere to the drug regimen
Key exclusion criteria (18 listed)
- Known contraindications, allergies, or hypersensitivities to any of the study medications or excipient as outlined in the investigators brochures (IBs), summary of product characteristics (SmPCs) or local package inserts for NEB and ZOF
- 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 within the last 6 months:
- myocardial infarction, unstable angina pectoris, percutaneous coronary intervention, bypass surgery, heart failure, hypertensive encephalopathy, cerebrovascular accident (stroke), or transient ischemic attack
- Patients with secondary hypertension of any etiology such as renal diseases, pheochromocytoma, or Cushing's syndrome
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zofenopril 30 mgFilm-Coated tablets administered as one single dose to be taken in the morning (from 6 am to 10 am) with no restriction on food intake | Drug | Zofenopril arm |
| Nebivolol 5 mgTablet administered as one single dose to be taken in the morning (from 6 am to 10 am) with no restriction on food intake | Drug | Nebivolol arm |
| Zofenopril 30 mg + Nebivolol 5 mgBoth Film coated tablets of Zofenopril 30 mg and Nebivolol 5 mg Tablets will be taken in the morning (from 6 am to 10 am) with no restriction on food intake | Drug | Nebivolol arm, Zofenopril arm |
Primary outcome
Change in Mean Sitting DBP Between Week 0 (Visit 2) and Week 8 (Visit 3)
Time frame: From Baseline (Week 0 - Visit 2) to week 8 (Visit 3)
To assess the antihypertensive efficacy of the extemporaneous combination of Nebivolol (NEB) 5 mg and Zofenopril (ZOF) 30 mg in lowering sitting diastolic blood pressure (DBP) from baseline (Visit 2) after 8 weeks of treatment (Visit 3), in patients with uncontrolled blood pressure (BP) who were previously treated with NEB or ZOF monotherapies for at least 4 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Massimo Volpe, Professor principal investigator
University "Sapienza" Rome
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Zofenopril 30 mg, Nebivolol 5 mg and Zofenopril 30 mg + Nebivolol 5 mg in people with Hypertension, run by Menarini International Operations Luxembourg SA at 1 site in Italy.
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 7 inclusion and 18 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 20 Sep 2024. 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 Italy. 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 20 Sep 2024). 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?
Change in Mean Sitting DBP Between Week 0 (Visit 2) and Week 8 (Visit 3) (time frame: From Baseline (Week 0 - Visit 2) to week 8 (Visit 3)). 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 20 Sep 2024.