Efficacy and Safety of Valsartan and Nebivolol/Valsartan in Hypertensive Patients With LVH (BVreduce)

A Prospective, Randomized, Open-Label, 13 to 14-week Study of the Efficacy and Safety of Valsartan and Nebivolol/Valsartan in Hypertensive Subjects With Left Ventricular Hypertrophy (LVH)

To assess the efficacy of Left Ventricular Hypertrophy (LVH) reduction and 24-hour blood pressure control of Valsartan 80mg or Nebivolol/Valsartan 5/80mg once daily as replacement therapy for currently treated or untreated hypertensive patients with LVH not at BP goal.

Study Overview

• Status: Completed
• Conditions: Blood Pressure; Hypertrophy, Left Ventricular; Hypertension Complicated
• Intervention / Treatment: Drug: Valsartan 80 mg

Detailed Description

The potential benefits of blood pressure reduction have been demonstrated in numerous large clinical trials. The most recent is the SPRINT Trial demonstrating that lower blood pressure goals can be achieved and are associated with a significant decrease in morbidity and mortality. The latest NHANES 2012 data reveal that less than 50% of patients that are aware of the elevated blood pressure and are being treated achieve blood pressure control. Treatment of hypertension in many patients (>70%) require treatment with more than one drug, increasing the likelihood of non-compliance and not achieving blood pressure goal. JNC 8 recommends the utilizing of combination therapy both for Stage I and Stage II Hypertensive patients.

Objectives of the study to assess the efficacy of LVH reduction and 24-hour blood pressure control of Valsartan 80mg and Nebivolol/Valsartan 5/80mg, once daily for the treatment of currently treated hypertensive patients with LVH.

The study will evaluate LVH reduction at 4 and 8 weeks as well as change from baseline in mean 24 hour ABPM SBP after 4 and 8 weeks of treatment with valsartan 80mg or nebivolol/valsartan 5/80mg

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Texas
    • Carrollton, Texas, United States, 75006
      • Trinity Hypertension & Metabolic Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Capable of reading, comprehending the consent process and providing written informed consent to participate in the study.
2. Male or female ≥ 18 years of age who are either newly diagnosed with HTN or who are currently being treated.
3. Patients must have a mean cuff sitting diastolic blood pressure cuff (DBP) > 90 mmHg and <105 mmHg (< 100 mmHg on prior treatment) and mean cuff sitting systolic blood pressure (SBP) <160 mmHg, at two consecutive qualifying visits during the placebo run in period.
4. Arm circumference < 45cm.
5. Compliance with single blind placebo capsules between V1 to 4 or 4X of 80-120%.
6. Women may be enrolled if the following criteria are met:

1.- Have a negative serum pregnancy test at screening 2.- Are not breastfeeding 3.- Do not plan to become pregnant during the study 4.- Have had a hysterectomy or tubal ligation at least 6 months prior to signing the informed consent form or 5.- Have been postmenopausal for at least 1 year or 6. - If they are of childbearing potential and will practice one of the following methods of birth control throughout the study: oral, patch, injectable, or implantable hormone contraception, intrauterine device, diaphragm plus spermicide or female condom plus spermicide. Abstinence, partner's vasectomy are not acceptable methods of contraception.

7. Diagnosis of Left Ventricular Hypertrophy (LVH).

Exclusion Criteria:

1. Known allergy or hypersensitivity to Beta-Blockers.
2. Known allergy or hypersensitivity to Angiotensin II Receptor Blockers.
3. Patients with severe hypertension (mean seated cuff DBP>115 mmHg or mean seated SBP> 180mmHg) or any form of secondary hypertension.
4. Patients within the past 6 months with a history of hypertensive encephalopathy, stroke or transient ischemic attack.
5. Patients within the last 6 months with a history of myocardial infarction, percutaneous transluminal coronary revascularization, coronary bypass graft, valvular surgery or unstable angina.
6. Patients with evidence of resting bradycardia (<50 bpm) via palpation.
7. Patients with a history of heart block greater than First Degree Sino-atrial Block. Wolff-Parkinson-White Syndrome, Sick Sinus Syndrome, Atrial Fibrillation, Atrial Flutter, Congestive Heart Failure, or other manifestations of clinically significant cardiac valvular disease.
8. Patients with hemodynamically significant cardiac valvular disease.
9. Patients with evidence of significant chronic renal impairment as indicated by a serum creatinine of > 2.5mg/dL.
10. Patients with evidence of liver disease as indicated by AST (SGOT) or ALT (SGPT) > 2.5 times or total bilirubin > 1.5 times, the upper limit of the laboratory normal range.
11. Patients who demonstrate other laboratory test values deviating from the normal range which are considered to be clinically significant by the investigator.
12. Patient with a history or presence of gastrointestinal disease which may interfere with drug absorption.
13. Patients with insulin and non-insulin dependent diabetes mellitus not controlled on diet, insulin, or oral hypoglycemics as defined by a HgA1c >10.
14. Severe psychological or emotional condition which may interfere with participation in the study.
15. History of or current use of illicit drugs or alcohol abuse.
16. Participation in a clinical trial and taking any investigational drug within 30 days prior to enrolling into the study (Screening Visit).
17. A physical condition that would limit accurate BP measurement.
18. Inability to swallow a tablet or capsule.
19. History of moderate or severe asthma or COPD.
20. Any other medical condition which, in the Investigator's opinion, may render the patient unable to complete the study or which would interfere with optimal participation in the study or produce significant risk to the patient.
21. Patients taking more than two blood pressure medications

22. Patients currently taking a beta blocker

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Valsartan Arm; Valsartan 80mg randomly assigned for 8 weeks to asses BP control with office and 24-hour ABPM and reduction of LVH	Drug: Valsartan 80 mg; Compare office and 24-hour Blood Pressure Control and regression of Left Ventricular Hypertrophy; Other Names: Nebivolol/Valsartan 5/80mg
Active Comparator: Nebivolol/Valsartan; Nebivolol/Valsartan 5/80mg randomly assigned for 8 weeks to asses Blood Pressure control with office and 24-hour Ambulatory Blood Pressure Monitoring and reduction of Left Ventricular Hypertrophy	Drug: Valsartan 80 mg; Compare office and 24-hour Blood Pressure Control and regression of Left Ventricular Hypertrophy; Other Names: Nebivolol/Valsartan 5/80mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LVH reduction at 4 weeks.	Reduction of Left ventricular hypertrophy from baseline compared to 4 weeks of treatment	4 weeks
24hr-ABPM measurement Change from baseline in mean 24 hour ABPM SBP	Reduction of Systolic BP over 24 hours baseline compared to 4 weeks of treatment	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LVH reduction at 8 weeks.	Reduction of Left ventricular hypertrophy from baseline compared to 8 weeks of treatment	8 weeks
24hr-Systolic ABPM measurement	Reduction of Systolic BP over 24 hours baseline compared to 8 weeks of treatment	8 weeks
24hr- DBP ABPM measurements	Mean change from baseline in trough DBP after 4 and 8 weeks of treatment with valsartan 80mg or nebivolol/valsartan 5/80mg	4 and 8 weeks
Office Blood Pressure measurements	Mean change from baseline in trough SBP after 4 and 8 weeks of treatment with valsartan 80mg or nebivolol/valsartan 5/80mg	4 and 8 weeks

Collaborators and Investigators

• Sponsor: Trinity Hypertension & Metabolic Research Institute
• Collaborators: Allergan Sales, LLC
• Investigators: Principal Investigator: Henry A Punzi, MD, UT Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2017
• Primary Completion (Actual): January 25, 2018
• Study Completion (Actual): January 25, 2018

Study Registration Dates

• First Submitted: June 6, 2017
• First Submitted That Met QC Criteria: June 6, 2017
• First Posted (Actual): June 8, 2017

Study Record Updates

• Last Update Posted (Actual): April 11, 2018
• Last Update Submitted That Met QC Criteria: April 10, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Cardiomegaly; Hypertrophy; Hypertrophy, Left Ventricular; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Adrenergic Agonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Adrenergic beta-Agonists; Adrenergic beta-1 Receptor Agonists; Valsartan; Nebivolol
• Other Study ID Numbers: BYS-IT-78

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No