HypertensionPhase 4BRAVENCT02398929

BRAVE Study With Uncontrolled Essential Hypertension (BRAVE Study)

A Phase 4 study testing Bisoprolol 2.5 mg in people with Hypertension, run by Chinese University of Hong Kong at 1 site in Hong Kong.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 79 years
Conditions the study is for: Hypertension
What is being tested?: Bisoprolol 2.5 mg
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 100 participants
Where: 1 siteHong Kong
Study dates: Jan 2013to 5 Jan 2021
Phase: Phase 4
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 79 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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)

Who cannot join

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;

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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.

Trial locations and contacts

1 site in 1 country.

Hong Kong1 site

Brian Tomlinson
Hong Kong

Other trials in Hong Kong

About this study

Official title: An Open Label, Pharmacogenetic Study of Bisoprolol Treatment in Patients With Uncontrolled Essential Hypertension (BRAVE)

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.

Read the 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.

Conditions: Hypertension
Being tested: Bisoprolol 2.5 mg, Placebo
Medical subject headings: Hypertension

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Bisoprolol 2.5 mgDrug
Also called Concor
Bisoprolol 2.5 mg will be given once daily
PlaceboDrug
Also called Run-in
Placebo tablets will be given once daily for 2 weeks during the run-in period.

Study groups in NCT02398929
Study group	Role	What they receive
Bisoprolol 2.5 mg	Other	Bisoprolol 2.5 mg will be given once daily following run-in placebo for 2 weeks Receives: Drug: Bisoprolol 2.5 mg; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 6 weeks

Secondary outcomes (3)

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.
Measured: 6 weeks
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.
Measured: 24 weeks
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.
Measured: 6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 20135 Jan 2021

First posted26 Mar 2015 (estimated)
Study startJan 2013
Primary completion5 Jan 2021
Study completion5 Jan 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (3)Papers the sponsor has linked to this study.
Other trials for HypertensionStudies of the same condition, open and under way.
More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 100 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02398929
Sponsor's protocol ID: EMR 200 006 621
Acronym: BRAVE
Status last verified: Jan 2021
First submitted: 17 Mar 2015
Last updated: 6 Jan 2021
Results posted: No
Data monitoring committee: No

Publications

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.
PubMed 17324745
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.
PubMed 20300048
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.
PubMed 15861037

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Hypertension trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open Label, Pharmacogenetic Study of Bisoprolol Treatment in Patients With Uncontrolled Essential Hypertension (BRAVE)
ClinicalTrials.gov ID: NCT02398929
Acronym / sponsor ID: BRAVE / EMR 200 006 621
Conditions: Hypertension
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 100 participants (actual)
Lead sponsor: Chinese University of Hong KongUniversity, hospital or other
Study start: Jan 2013
Primary completion: 5 Jan 2021 (actual)
Study completion: 5 Jan 2021 (actual)
First posted: 26 Mar 2015 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Bisoprolol 2.5 mg	Other	Drug: Bisoprolol 2.5 mg, Drug: PlaceboBisoprolol 2.5 mg will be given once daily following run-in placebo for 2 weeks

Who may qualify

Ages: 18 to 79 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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)

Key exclusion criteria (12 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Bisoprolol 2.5 mgAlso: ConcorBisoprolol 2.5 mg will be given once daily	Drug	Bisoprolol 2.5 mg
PlaceboAlso: Run-inPlacebo tablets will be given once daily for 2 weeks during the run-in period.	Drug	Bisoprolol 2.5 mg

Primary outcome

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.
Time frame: 6 weeks
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.

3 secondary outcomes

Change of blood pressure from baseline to 6 weeks by clinic sitting blood pressure according to other genotypes.
Time frame: 6 weeks
Change of blood pressure from baseline to 24 weeks by clinic sitting blood pressure according to other genotypes.
Time frame: 24 weeks
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.
Time frame: 6 weeks

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2021.
Background: PubMed 17324745Hiltunen 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.
Background: PubMed 20300048Suonsyrja 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.
Background: PubMed 15861037de 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.

Related trials for Hypertension

RecruitingPhase 2/3
The Effect of Additive On-Demand Sildenafil vs. Dextrose Candy on Maximum Exercise Capacity in Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension (PAH) (WHO Group 1 PH)
Not yet recruiting
Multimodal AI-Driven Out-of-Hospital Management for Hypertension and Cardiometabolic Risk
Hypertension, Hyperglycemia
Active, not recruiting
Optimizing Prescribing Decisions for Hospitalized Older Adults With Chronic Conditions
Prescribing Decisions, Diabetes
Enrolling by invitationObservational study
WSACS 2026 Delphi Consensus on the Practical Management of Intra-abdominal Hypertension and Abdominal Compartment Syndrome
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Not yet recruitingPhase 4
Sacubitril/Valsartan vs Standard Treatment for Preventing Atrial Fibrillation Recurrence After Catheter Ablation in Persistent Atrial Fibrillation Patients With Without Hypertension
Atrial Fibrillation (Persistent), Catheter Ablation

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Brian Tomlinson, MD principal investigator

Chinese University of Hong Kong

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Bisoprolol 2.5 mg in people with Hypertension, run by Chinese University of Hong Kong at 1 site in Hong Kong.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: 6 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02398929, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2021.