BRAVE Study With Uncontrolled Essential Hypertension (BRAVE Study)

NCT02398929 | Completed Phase 4

• 1 other identifier: EMR 200 006 621
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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 After informed consent is obtained, subjects will be withdrawn from previous antihypertensive therapy and given placebo for at least 2 weeks.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.

Conditions

Hypertension

Outcome Measures

Primary Outcomes (1)

• 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.

  6 weeks

Secondary Outcomes (3)

• Change of blood pressure from baseline to 6 weeks by clinic sitting blood pressure according to other genotypes.

  6 weeks

• Change of blood pressure from baseline to 24 weeks by clinic sitting blood pressure according to other genotypes.

  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.

  6 weeks

Study Arms (1)

Bisoprolol 2.5 mg

OTHER

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

Drug: Bisoprolol 2.5 mg; Drug: Placebo

Interventions

Bisoprolol 2.5 mg DRUG

Bisoprolol 2.5 mg will be given once daily

Also known as: Concor

Bisoprolol 2.5 mg

Placebo DRUG

Placebo tablets will be given once daily for 2 weeks during the run-in period.

Also known as: Run-in

Bisoprolol 2.5 mg

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Chinese University of Hong Kong: lead

Study Sites (1)

Brian Tomlinson

Hong Kong, Hong Kong

Location

Related Publications (3)

• 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.

  PMID: 17324745 BACKGROUND

• 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.

  PMID: 20300048 BACKGROUND

• 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.

  PMID: 15861037 BACKGROUND

MeSH Terms

Conditions

Hypertension

Interventions

Bisoprolol

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines

Study Officials

• Brian Tomlinson, MD

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 17, 2015
• First Posted: March 26, 2015
• Study Start: January 1, 2013
• Primary Completion: January 5, 2021
• Study Completion: January 5, 2021
• Last Updated: January 6, 2021

Record last verified: 2021-01

Locations

HK (1)