NCT06104423

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

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

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 266 (actual)
• Sponsor: Menarini International Operations Luxembourg SA · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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

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

Interventions

Type	Name	Description
DRUG	Nebivolol 5 mg	1 tablet of study medication (5mg) to be administered orally according to instructions of Investigator.
DRUG	Ramipril 2.5/5/10 mg	1 tablet of study medication (2.5mg or 5mg or 10mg) to be administered orally according to instructions of Investigator.

Timeline

• Start date: 2023-10-02
• Primary completion: 2024-02-19
• Completion: 2024-02-19
• First posted: 2023-10-27
• Last updated: 2025-04-24
• Results posted: 2025-04-24

Locations

1 site across 1 country: Hungary