Association Between Genetic Polymorphism of Beta-adrenergic Receptor and Effects of Bisoprolol in Korean Heart Failure Patients. (ABBA)

Merck KGaA (EMD Serono)

Status and phase

Completed

Phase 4

Conditions

Chronic Heart Failure

Treatments

Drug: Bisoprolol

Study type

Interventional

Funder types

Industry

Identifiers

NCT01104558

EMD084000-500

Details and patient eligibility

About

At present, there is some clinical data for different functional response to beta-blockers associated with beta-adrenergic receptor polymorphisms. But there has been no data reported, about the incidence of beta-adrenergic receptor polymorphism and association with beta-adrenergic receptor polymorphism and response to beta-blocker therapy in Korean heart failure (HF) subjects. This single-arm, open-label, multicentric study is designed with the purpose of analyzing the association between genetic polymorphism of beta-adrenergic receptor and the effects of beta-blocker (bisoprolol) in Korean HF subjects.

Full description

Heart failure impairs the quality of life of an individual and is considered to be the main cause of morbidity and mortality. Prognosis of HF subjects depends on severity, age and sex. Subjects with HF require lifelong treatment. Pharmacological treatment aims to improve both the quality of life and survival of HF subjects.

OBJECTIVES:

Primary objective:

To analyze the association between genetic polymorphism of beta-adrenergic receptor and the effects of beta-blocker (bisoprolol) in Korean HF subjects

Secondary objective:

The frequency of polymorphism of beta adrenergic receptor in Korean HF subjects
To evaluate change from baseline in 6-minute walking test, heart rate (HR), blood pressure (BP), pro B-type natriuretic peptide (BNP) level at week 26 or End of Treatment (EOT)
To compare frequency and duration of hospitalization due to heart failure

The method involved in this study will be as follows:

Initial evaluation of HF subjects
Blood genomic deoxyribonucleic acid (DNA) isolation and collection
Bisoprolol treatment as add on therapy with standard treatment for HF subject for 6 months
Genotype of beta adrenergic receptor polymorphism
Follow up evaluation of treated subjects

Bisoprolol will be given in a starting dose of 1.25 milligram (mg) once daily for two weeks and if it is well tolerated, the dose will be increased to 2.5 mg, 3.75 mg, 5 mg once daily in intervals of two weeks, 5 mg daily as a maintenance therapy. If the subject is tolerable, the dose can be increased as 10 mg/day as maximum dose.

Enrollment

100 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

>18 years of age and <80 years of age
Chronic heart failure subjects with stable clinical condition
New York Heart Association (NYHA) functional classification II-III
Left ventricular ejection fraction (LVEF) ≤45%

Exclusion criteria

NYHA functional classification IV
Acute myocardial infarction, Unstable Angina Pectoris, Coronary artery bypass graft, Percutaneous coronary intervention (PCI), Valve surgery in the preceding 3 months
Hypersensitivity to bisoprolol or any of the Concor excipients
Subjects with over mild valvular stenosis and severe(Grade III/IV) pulmonary insufficiency
Systolic Blood Pressure <90 millimeters of mercury (mmHg) at screening
Resting Heart Rate <55 beats per minute (bpm) confirmed by electrocardiogram (ECG) at screening
Subjects who are taking concomitant drug which can have drug-drug interaction (DDI) with bisoprolol
Woman of childbearing age without effective contraception measures, or who are pregnant or lactating