Clinical trial NCT06938516: Prospective Observational Study On The Impact Of Nebilet In Blood Pressure Control In Hypertensive Patients (HYIMPACT)
Official title: IMPACT of Nebilet in Blood Pressure Control in Patients With HYpertension: An Observational, Longitudinal Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hypertension
Keywords: High Blood Pressure
Nebivolol in high blood pressure
Use of Nebilet in high blood pressure
Lead sponsor: A.Menarini Asia-Pacific Holdings Pte Ltd
Sponsor class: INDUSTRY
First posted: 2025-04-22
Enrollment: 4537
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients from South-East Asia countries will be enrolled.

The names of the participating countries are as follows:

1. Taiwan
2. Indonesia
3. South Korea
4. Philippines
5. Thailand
6. Malaysia
7. Vietnam

Brief summary: The HYIMPACT study (IMPACT of Nebilet® in Blood Pressure Control in Patients with Hypertension) is a multinational, multicenter, observational, prospective, longitudinal real-world evidence study designed to assess the effectiveness and safety of Nebilet® (nebivolol) in hypertensive patients. The study aims to evaluate changes in systolic and diastolic blood pressure from baseline to 12, 24, and 36 months, as well as treatment adherence, quality of life, prescription patterns, and cardiovascular outcomes.

A total of approximately 5,000 hypertensive patients with or without cardiovascular comorbidities will be enrolled across seven Asian countries (Malaysia, Indonesia, the Philippines, Korea, Vietnam, Thailand, and Taiwan). Patients newly initiated on Nebilet®-based treatment or already receiving Nebilet® for no more than two weeks prior to screening will be eligible for inclusion.

Patients will be followed at regular intervals for up to three years. The study will also assess the correlation between home and office blood pressure measurements and compare Nebilet® monotherapy with combination therapy in achieving target blood pressure control. The findings from this study will provide real-world insights into the clinical management of hypertension with Nebilet® and its impact on patient outcomes.

Detailed description: Introduction. Hypertension remains one of the leading risk factors for cardiovascular morbidity and mortality worldwide, contributing significantly to the burden of stroke, heart failure, and other cardiovascular diseases. Despite advancements in antihypertensive therapies, real-world data on long-term blood pressure control, treatment adherence, and patient-reported outcomes remain insufficient, particularly in diverse populations across Asia. While clinical trials have established the efficacy of various antihypertensive agents, the applicability of these findings to routine clinical practice remains unclear. Beta-blockers, particularly nebivolol, a third-generation β1-selective adrenergic antagonist with nitric oxide-mediated vasodilatory properties, have demonstrated favorable hemodynamic effects, improved vascular function, and better tolerability compared to traditional beta-blockers. However, there is a lack of robust real-world evidence assessing its long-term impact on blood pressure control and cardiovascular outcomes.

The HYIMPACT study is a multinational, multicenter, observational, longitudinal study designed to evaluate the real-world effectiveness, safety, and adherence of Nebilet® (nebivolol) in hypertensive patients across seven Asian countries. This study will provide insights into the clinical utility of Nebilet® in achieving sustained blood pressure control over time, while also assessing the influence of cardiovascular risk factors on treatment outcomes. By systematically collecting data from patients in routine clinical settings, HYIMPACT aims to bridge the gap between controlled clinical trials and real-world practice, offering valuable evidence to optimize hypertension management strategies.

Study Objectives. HYIMPACT aims to assess the impact of Nebilet®-based treatment on systolic and diastolic blood pressure control from baseline to 12, 24, and 36 months. The study will determine the proportion of patients achieving target blood pressure levels (\<140/90 mmHg) and evaluate adherence using the Morisky 8-Item Medication Adherence Scale (MMAS). Additionally, the study will compare the effectiveness of Nebilet® monotherapy versus combination therapy in achieving blood pressure control. Patient-reported outcomes will be analyzed using the SF-36 and MINICHAL questionnaires, providing insights into the impact of treatment on quality of life. The study will also assess the correlation between home and office blood pressure measurements and investigate the association between Nebilet® use and major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and cardiovascular mortality.

Study Design and Population. HYIMPACT is an observational, prospective, longitudinal study enrolling approximately 5,000 hypertensive patients across Malaysia, Indonesia, the Philippines, Korea, Vietnam, Thailand, and Taiwan. Eligible patients will be adults aged 18 years or older with newly diagnosed or uncontrolled hypertension, defined as an office systolic blood pressure of at least 140 mmHg and/or diastolic blood pressure of at least 90 mmHg at screening. Patients may be included if they have either been newly prescribed Nebilet® or have been on Nebilet®-based treatment for no more than two weeks prior to enrollment. Individuals with recent major cardiovascular events within the last three months, severe heart failure classified as NYHA Class IV, or contraindications to Nebilet® as per the Summary of Product Characteristics will be excluded. The study will involve 300 to 500 physicians, ensuring representation across a wide range of real-world clinical settings.

Variables to be Collected. The study will systematically collect patient demographic and clinical data, including medical history, cardiovascular risk factors such as diabetes, obesity, and hypercholesterolemia, and medication use. Blood pressure measurements will be recorded at baseline and at each follow-up visit, with additional data collected on prescription patterns, dose adjustments, and patient adherence. Laboratory parameters, including lipid profiles, glycated hemoglobin (HbA1c), and renal function markers, will be documented when available. Cardiovascular outcomes such as MACE, including myocardial infarction, stroke, and cardiovascular mortality, will be monitored throughout the study.

Follow-Up and Data Collection. Patients will be evaluated at baseline and followed up at 12, 24, and 36 months. Blood pressure will be measured at each visit using standardized protocols, and home blood pressure readings will be encouraged to assess their correlation with office measurements. Patient-reported quality of life and adherence assessments will be conducted using validated questionnaires. Any adverse events, including treatment-emergent and serious adverse events, will be documented. Data will be recorded in an electronic case report form (eCRF) using the CLINYTICS platform, ensuring consistency and standardization across study sites.

Quality Control Measures. To ensure high data quality, the study will implement standardized definitions and data collection procedures across all sites. Investigators will receive training on study protocols, and automated validation checks within the eCRF system will help identify inconsistencies. Regular site audits will be conducted to monitor compliance, and periodic investigator meetings will be held to review study progress. Ethics committee approvals will be obtained in each participating country, and all data will be handled in compliance with Good Clinical Practice (GCP) guidelines and local data protection regulations.

Statistical Analysis. Continuous variables such as blood pressure values will be summarized as means with standard deviations, while categorical variables will be presented as frequencies and percentages. Changes in systolic and diastolic blood pressure over time will be analyzed using paired t-tests and repeated measures ANOVA, with non-parametric alternatives applied when normality assumptions are not met. The effectiveness of Nebilet® monotherapy versus combination therapy will be assessed using logistic regression for categorical outcomes and ANOVA for continuous variables. Cox proportional hazards models will evaluate the association between Nebilet® treatment and cardiovascular outcomes. Pearson correlation coefficients will be used to analyze the relationship between home and office blood pressure measurements, and structural equation modelling (SEM) will be applied to address potential regression dilution bias.

Study Governance and Data Ownership. HYIMPACT is an investigator-led study with data collection coordinated through a centralized electronic data management system. Each participating physician retains ownership of individual patient data, while consolidated and anonymized study results will be used for scientific analysis and publication. Patient confidentiality will be strictly maintained through secure data storage, anonymization, and regulatory compliance with local data protection laws.

The findings from HYIMPACT will provide valuable insights into the long-term real-world effectiveness of Nebilet® in managing hypertension. By analyzing treatment adherence, quality of life, and cardiovascular outcomes over time, this study will contribute to optimizing hypertension treatment strategies and improving patient care across diverse healthcare settings.

Eligibility criteria: Inclusion Criteria:

* Adult patients ≥ 18 years of age with either newly diagnosed or uncontrolled hypertension (office SBP ≥140 and/or DBP ≥90 mmHg recorded at the time of screening) as per ESC/ESH guidelines 2018.
* Hypertensive patients - with or without cardiovascular comorbidities (such as coronary artery disease, heart failure, peripheral artery disease, cerebrovascular disease, arrhythmias, and valvular heart disease) - who are newly prescribed or are already on Nebilet based treatment (no more than for 2 weeks at screening).
* Hypertensive patients willing to provide consent to participate in the study.
* Women of reproductive age who are willing to use adequate means of contraception.

Exclusion Criteria:

* Patients with recent cardiovascular event within less than 3 months.
* Patient with heart failure based on New York Heart Association (NYHA) Functional Classification- Class IV.
* Patients with contraindications to Nebilet based treatment as per respective Summary of Product Characteristic (SmPC) which in the treating physician's judgment may jeopardize the subject by his or her participation in this study or may hamper his or her ability to perform and complete procedures required in the study.

Primary outcomes:
measure: Change in mean sitting systolic blood pressure from baseline to one year of treatment in hypertensive patients on Nebilet based treatment.
timeFrame: Baseline to 12 months
Secondary outcomes:
measure: To assess the impact of Nebilet based treatment in changing diastolic BP (DBP) in hypertensive patients in real-world setting from baseline to one year of treatment.
timeFrame: Baseline to 12 months
measure: Change in mean sitting SBP and DBP from baseline to two years and at the end of three years in hypertensive patients on Nebilet based treatment.
timeFrame: Baseline to 24 months and 36 months
measure: To evaluate the proportions of patients achieving target BP goal (<140/90 mm Hg) at different time points (12 months, 24 months, and 36 months of treatment) with Nebilet based as combination treatment.
timeFrame: 12, 24 and 36 months
measure: To assess the association of various risk factors (diabetes, obesity, and hypercholesterolemia) on development of major cardiac events in patients who achieve BP control over a period of 36 months.
timeFrame: 36 months
measure: To study the prescription patterns of Nebilet®-based treatment in terms of frequency per day in real-world settings.
timeFrame: 36 months
measure: To study the prescription patterns of Nebilet®-based treatment in terms of dose in milligrams in real-world settings.
timeFrame: 36 months
measure: To study the prescription patterns or Nebilet®-based treatment in terms of treatment duration in months, in real-world settings.
timeFrame: 36 months
measure: To assess the impact of Nebilet®-based treatment on the quality-of-life of patients using MINICHAL questionnaire.
timeFrame: Baseline, 12 months, 24 months and 36 months
measure: To assess the patient-reported outcomes using a short form 36 health survey (SF-36 questionnaire) .
timeFrame: Baseline, 12 month, 24 month, and 36 month
measure: To assess patient adherence to treatment by an 8-item Morisky Medication Adherence Scale every 3 months after baseline, till 36 months.
timeFrame: 3 month, 6 month, 9 month, 12 month, 15 month, 18 month, 21 month, 24 month, 27 month, 30 month, 33 month, 36 month
Other outcomes:
Locations:
city: Semarang
country: Indonesia
facility: Telogorejo Hospital
state: Central Java
city: Yogyakarta
country: Indonesia
facility: Bethesda Hospital
state: Central Java
city: Yogyakarta
country: Indonesia
facility: Panti rapih Hospital
state: Central Java
city: Surabaya
country: Indonesia
facility: Husada Utama Hospital
state: East Java
city: Surabaya
country: Indonesia
facility: Premere Surabaya Hospital
state: East Java
city: Selatan
country: Indonesia
facility: Bidakara Medical Centre
state: Jakarta
city: Pekanbaru
country: Indonesia
facility: PT Ekamas International Hospital
state: Riau
city: Makassar
country: Indonesia
facility: Stella Maris Hospital
state: South Sulawasi
city: Palembang
country: Indonesia
facility: Bukit Asam Medika Hospital
state: South Sumatra
city: Bandung
country: Indonesia
facility: Advent Hospital
state: West Java
city: Bandung
country: Indonesia
facility: Borromeus Hospital
state: West Java
city: Sukabumi
country: Indonesia
facility: RSUD Syamsudin Hospital
state: West Java
city: Padang
country: Indonesia
facility: Semen Padang Hospital
state: West Sumatra
city: Jakarta
country: Indonesia
facility: National Cardiovascular Center Harapan Kita Hospital
city: Jakarta
country: Indonesia
facility: Metropolitan Medical Centre Hospital
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
state: Jongno District Seoul
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Seoul
country: Korea, Republic of
facility: Eunpyeong St. Mary's Hospital
city: Seremban
country: Malaysia
facility: Columbia Asia Hospital Seremban
state: Negeri Sembilan
city: Seremban
country: Malaysia
facility: Mawar Medical Centre
state: Negeri Sembilan
city: Klang
country: Malaysia
facility: Bukit Tinggi Medical Centre
state: Selangor
city: Kuala Lumpur
country: Malaysia
facility: DrThong,Leow,Chiam & Partners
city: Kuala Lumpur
country: Malaysia
facility: Klinik Pembangunan Sdn. Bhd
city: Kuala Lumpur
country: Malaysia
facility: Pantai HKL
city: Lipa
country: Philippines
facility: Mary Mediatrix Medical Center
state: Batangas
city: Quezon City
country: Philippines
facility: Veterans Memorial Medical Center
state: Manila
city: New Taipei
country: Taiwan
facility: Far Eastern Memorial Hospital (FEMH)
state: Banqiao
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital (CCH)
state: Changhua County
city: Pozi
country: Taiwan
facility: Chang Gung Memorial Hospital-Chiayi branch (CGMH-CY)
state: Chiayi County
city: Taoyuan
country: Taiwan
facility: Chung Gung Memorial Hospital-Linkou Branch (CGMH-LK)
state: Guishan District
city: Hualien City
country: Taiwan
facility: Hualien Tzu-Chi Hospital (HTCH)
state: Hualien County
city: Taipei
country: Taiwan
facility: Asia University Hospital (AUH)
state: Nangang Dist.
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital (NCKUH)
state: North District
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital (KMUH)
state: Sanmin District
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital (TMUH)
state: Xinyi District
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital (TVGH)
state: Xitun District
city: Tainan
country: Taiwan
facility: Chi-Mei Medical Center (CMC)
state: Yongkang Dist.
city: Taipei
country: Taiwan
facility: MacKay Memorial Hospital (MMH)
state: Zhongshan District
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital (NTUH)
state: Zhongzheng District
city: Dusit
country: Thailand
facility: Vajira Hospital Namindradhiraj University
state: Bangkok
city: Nong Chok
country: Thailand
facility: Wetchakarunrasm Hospital
state: Bangkok
city: Chon Buri
country: Thailand
facility: Burapha University
state: Chonburi
city: Lopburi
country: Thailand
facility: Anand Mahidhol Hospital
state: Lopaburi
city: Chiang Mai
country: Thailand
facility: Chiang Mai University
city: Nonthaburi
country: Thailand
facility: Central Chet Institute
city: Can Tho
country: Vietnam
facility: CanTho General Hospital
city: Hanoi
country: Vietnam
facility: Hanoi Heart Hospital
city: Ho Chi Minh
country: Vietnam
facility: Cho Ray Hospital
city: Hue
country: Vietnam
facility: Hue Central Hospital
Study officials:
affiliation: A. Menarini Asia-Pacific Holding Pte Ltd
name: Dr Radhika Mehta
role: STUDY_DIRECTOR
References: