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BRAVE Study With Uncontrolled Essential Hypertension (BRAVE Study) (BRAVE)

Primary Purpose

Hypertension

Status
Completed
Phase
Phase 4
Locations
Hong Kong
Study Type
Interventional
Intervention
Bisoprolol 2.5 mg
Placebo
Sponsored by
Chinese University of Hong Kong
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypertension

Eligibility Criteria

18 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with essential hypertension
  • For uncomplicated hypertensive patients on no antihypertensive treatment, sitting clinic systolic blood pressure of 140-169 mmHg and / or a sitting clinic diastolic blood pressure of 90-109 mmHg.
  • For patients with diabetes mellitus or with chronic kidney disease, sitting clinic systolic blood pressure of 130-169 mmHg and / or a sitting clinic diastolic blood pressure of 80-109 mmHg.
  • Patient has a heart rate >70 b/min at baseline (before starting bisoprolol treatment)

Exclusion Criteria:

  • Secondary Hypertension
  • Pregnant or lactating women and women with childbearing potential not using adequate method of contraception or agreeing to maintain sexual abstinence throughout the study;
  • Unstable angina, history of myocardial infarction, stroke or coronary heart disease (coronary by-pass or angioplasty) in the previous 3 months;
  • Heart failure (New York Heart Association [NYHA] III-IV);
  • Haemodynamically relevant aortic or mitral valve disease;
  • Obstructive hypertensive cardiomyopathy;
  • Symptomatic bradycardia, second or third degree atrio-ventricular (AV) block, sick sinus syndrome, sinoatrial block, or heart rate <70 b/min at baseline (before starting bisoprolol treatment);
  • Primary hyperaldosteronism;
  • Renal artery stenosis;
  • Impairment of hepatic or renal function as defined by liver function values of ALT ≥1.5-fold the upper normal limit or serum creatinine >150 µmol/L or upon investigator decision;
  • History of intolerance to beta-blockers the drug classes used in the study.
  • Patients with a known contraindication to beta-blockers, e.g. bradycardia, asthma, severe peripheral vascular disease.

Sites / Locations

  • Brian Tomlinson

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Bisoprolol 2.5 mg

Arm Description

Bisoprolol 2.5 mg will be given once daily following run-in placebo for 2 weeks

Outcomes

Primary Outcome Measures

Influence of the two common polymorphisms in the beta1-adrenoceptor (ADRB1) gene on changes in sitting clinic blood pressure after 6 weeks treatment with bisoprolol 2.5 mg daily.
Subjects will be divided according to the Gly389Arg and Ser49Gly polymorphisms in ADRB1 gene and the clinic blood pressure changes at 6 weeks compared between these groups.

Secondary Outcome Measures

Change of blood pressure from baseline to 6 weeks by clinic sitting blood pressure according to other genotypes.
Patients will be divided into groups according to genotypes of the Fok+/Fok- polymorphism in the G-protein alpha subunit (GNAS) gene and the T393C polymorphism in the G-protein alpha subunit 1 (GNAS1) gene, and changes in blood pressure after 6 weeks treatment compared.
Change of blood pressure from baseline to 24 weeks by clinic sitting blood pressure according to other genotypes.
Patients will be divided into groups according to genotypes of the Fok+/Fok- polymorphism in the G-protein alpha subunit (GNAS) gene and the T393C polymorphism in the G-protein alpha subunit 1 (GNAS1) gene, and changes in blood pressure after 24 weeks treatment compared.
Influence of the two common polymorphisms in the beta1-adrenoceptor (ADRB1) gene on changes in ambulatory blood pressure (ABP) after 6 weeks treatment with bisoprolol 2.5 mg daily.
Subjects will be divided according to the Gly389Arg and Ser49Gly polymorphisms in the ADRB1 gene and the ambulatory blood pressure changes at 6 weeks compared between these groups.

Full Information

First Posted
March 17, 2015
Last Updated
January 4, 2021
Sponsor
Chinese University of Hong Kong
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1. Study Identification

Unique Protocol Identification Number
NCT02398929
Brief Title
BRAVE Study With Uncontrolled Essential Hypertension (BRAVE Study)
Acronym
BRAVE
Official Title
An Open Label, Pharmacogenetic Study of Bisoprolol Treatment in Patients With Uncontrolled Essential Hypertension (BRAVE)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
January 2013 (undefined)
Primary Completion Date
January 5, 2021 (Actual)
Study Completion Date
January 5, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese University of Hong Kong

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is an open-label, placebo run-in study to investigate the genetic and biomedical predictors of blood pressure response to bisoprolol. After informed consent is obtained, subjects will be withdrawn from previous antihypertensive therapy and given placebo for at least 2 weeks. Compliance will be assessed using pill counting, and any subject will a compliance less than 80% during the placebo run-in period will be excluded from the study. Bisoprolol 2.5 mg will be given once daily for 6 weeks. At baseline and after 6 weeks on bisoprolol 2.5 mg the clinic sitting blood pressure, 24-hour ambulatory blood pressure (if the patient is willing to do this), clinical characteristics and biochemical profile will be measured. Central aortic blood pressure will be measured with the A-PULSE device at baseline and after 6 weeks treatment. After completing 6 weeks treatment with bisoprolol 2.5 mg daily, the patient will continue treatment with bisoprolol for a total of 24 weeks unless there is any adverse event that requires discontinuation of bisoprolol.
Detailed Description
Patients with uncontrolled essential hypertension aged 18-79 years on no antihypertensive treatment with sitting clinic systolic blood pressure of 140-169 mmHg and/or a sitting clinic diastolic blood pressure of 90-109 mmHg, or for patients with diabetes mellitus or with chronic kidney disease with sitting clinic systolic blood pressure of 130-169 mmHg and / or a sitting clinic diastolic blood pressure of 80-109 mmHg and heart rate > 70 at baseline (before starting bisoprolol treatment) will be enrolled. Patients on other antihypertensive treatments who are experiencing side effects or whose blood pressure may not be well controlled can also enter if they can continue on a stable dose of a calcium channel blocker, either amlodipine or nifedipine retard throughout the study. Patients will be treated with bisoprolol 2.5mg daily for a total of 26 weeks. The primary endpoint will be the influence of common genetic polymorphisms on clinic sitting blood pressure or ambulatory blood pressure (ABP) response to bisoprolol 2.5 mg after 6 weeks treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bisoprolol 2.5 mg
Arm Type
Other
Arm Description
Bisoprolol 2.5 mg will be given once daily following run-in placebo for 2 weeks
Intervention Type
Drug
Intervention Name(s)
Bisoprolol 2.5 mg
Other Intervention Name(s)
Concor
Intervention Description
Bisoprolol 2.5 mg will be given once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Run-in
Intervention Description
Placebo tablets will be given once daily for 2 weeks during the run-in period.
Primary Outcome Measure Information:
Title
Influence of the two common polymorphisms in the beta1-adrenoceptor (ADRB1) gene on changes in sitting clinic blood pressure after 6 weeks treatment with bisoprolol 2.5 mg daily.
Description
Subjects will be divided according to the Gly389Arg and Ser49Gly polymorphisms in ADRB1 gene and the clinic blood pressure changes at 6 weeks compared between these groups.
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Change of blood pressure from baseline to 6 weeks by clinic sitting blood pressure according to other genotypes.
Description
Patients will be divided into groups according to genotypes of the Fok+/Fok- polymorphism in the G-protein alpha subunit (GNAS) gene and the T393C polymorphism in the G-protein alpha subunit 1 (GNAS1) gene, and changes in blood pressure after 6 weeks treatment compared.
Time Frame
6 weeks
Title
Change of blood pressure from baseline to 24 weeks by clinic sitting blood pressure according to other genotypes.
Description
Patients will be divided into groups according to genotypes of the Fok+/Fok- polymorphism in the G-protein alpha subunit (GNAS) gene and the T393C polymorphism in the G-protein alpha subunit 1 (GNAS1) gene, and changes in blood pressure after 24 weeks treatment compared.
Time Frame
24 weeks
Title
Influence of the two common polymorphisms in the beta1-adrenoceptor (ADRB1) gene on changes in ambulatory blood pressure (ABP) after 6 weeks treatment with bisoprolol 2.5 mg daily.
Description
Subjects will be divided according to the Gly389Arg and Ser49Gly polymorphisms in the ADRB1 gene and the ambulatory blood pressure changes at 6 weeks compared between these groups.
Time Frame
6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with essential hypertension For uncomplicated hypertensive patients on no antihypertensive treatment, sitting clinic systolic blood pressure of 140-169 mmHg and / or a sitting clinic diastolic blood pressure of 90-109 mmHg. For patients with diabetes mellitus or with chronic kidney disease, sitting clinic systolic blood pressure of 130-169 mmHg and / or a sitting clinic diastolic blood pressure of 80-109 mmHg. Patient has a heart rate >70 b/min at baseline (before starting bisoprolol treatment) Exclusion Criteria: Secondary Hypertension Pregnant or lactating women and women with childbearing potential not using adequate method of contraception or agreeing to maintain sexual abstinence throughout the study; Unstable angina, history of myocardial infarction, stroke or coronary heart disease (coronary by-pass or angioplasty) in the previous 3 months; Heart failure (New York Heart Association [NYHA] III-IV); Haemodynamically relevant aortic or mitral valve disease; Obstructive hypertensive cardiomyopathy; Symptomatic bradycardia, second or third degree atrio-ventricular (AV) block, sick sinus syndrome, sinoatrial block, or heart rate <70 b/min at baseline (before starting bisoprolol treatment); Primary hyperaldosteronism; Renal artery stenosis; Impairment of hepatic or renal function as defined by liver function values of ALT ≥1.5-fold the upper normal limit or serum creatinine >150 µmol/L or upon investigator decision; History of intolerance to beta-blockers the drug classes used in the study. Patients with a known contraindication to beta-blockers, e.g. bradycardia, asthma, severe peripheral vascular disease.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brian Tomlinson, MD
Organizational Affiliation
Chinese University of Hong Kong
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brian Tomlinson
City
Hong Kong
Country
Hong Kong

12. IPD Sharing Statement

Citations:
PubMed Identifier
17324745
Citation
Hiltunen TP, Suonsyrja T, Hannila-Handelberg T, Paavonen KJ, Miettinen HE, Strandberg T, Tikkanen I, Tilvis R, Pentikainen PJ, Virolainen J, Kontula K. Predictors of antihypertensive drug responses: initial data from a placebo-controlled, randomized, cross-over study with four antihypertensive drugs (The GENRES Study). Am J Hypertens. 2007 Mar;20(3):311-8. doi: 10.1016/j.amjhyper.2006.09.006. Erratum In: Am J Hypertens. 2018 Nov 13;31(12):1333.
Results Reference
background
PubMed Identifier
20300048
Citation
Suonsyrja T, Donner K, Hannila-Handelberg T, Fodstad H, Kontula K, Hiltunen TP. Common genetic variation of beta1- and beta2-adrenergic receptor and response to four classes of antihypertensive treatment. Pharmacogenet Genomics. 2010 May;20(5):342-5. doi: 10.1097/FPC.0b013e328338e1b8.
Results Reference
background
PubMed Identifier
15861037
Citation
de Groote P, Helbecque N, Lamblin N, Hermant X, Mc Fadden E, Foucher-Hossein C, Amouyel P, Dallongeville J, Bauters C. Association between beta-1 and beta-2 adrenergic receptor gene polymorphisms and the response to beta-blockade in patients with stable congestive heart failure. Pharmacogenet Genomics. 2005 Mar;15(3):137-42. doi: 10.1097/01213011-200503000-00001.
Results Reference
background

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BRAVE Study With Uncontrolled Essential Hypertension (BRAVE Study)

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