Effectiveness and Safety of Combination of Nebivolol and Zofenopril in Hypertensive patIents Versus Each Monotherapy
Condition: Hypertension
MeSH terms: Hypertension
Study type: Interventional
Phase: Phase 4

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
    

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 (ACE-i) 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.
    

Intervention name(s): Zofenopril 30 mg; Nebivolol 5 mg; Zofenopril 30 mg + Nebivolol 5 mg
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 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; Tablet administered as one single dose to be taken in the morning (from 6 am to 10 am) with no restriction on food intake; 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
Intervention MeSH terms: Nebivolol; Zofenopril; Captopril
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Intervention 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)
Primary purpose: Treatment
Keywords: Hypertension; Combination Therapy; Zofenopril; Nebivolol; Fixed Dose Combination