Clinical trial NCT01104558: Association Between Genetic Polymorphism of Beta-adrenergic Receptor and Effects of Bisoprolol in Korean Heart Failure Patients.
Official title: Association Between Beta-1 and Beta-2 Adrenergic Receptor Polymorphism and Beta-blocker (Bisoprolol) Therapy in Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Heart Failure
Keywords: Bisoprolol
Chronic Heart failure
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
Collaborators: name: Merck Ltd.
First posted: 2010-04-15
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Echocardiographic Left Ventricular Ejection Fraction (LVEF) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or End of Treatment (EOT)
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of G Protein-coupled Receptor Kinase 5 (GRK5)-AG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
Secondary outcomes:
measure: Number of Participants With Hospitalization Due to Heart Failure
timeFrame: Baseline to Week 26 (or EOT)
measure: Duration of Hospitalization Due to Heart Failure
timeFrame: Baseline to Week 26 (or EOT)
measure: Change From Baseline in 6-minute Walking Test (6-MWT) Distance According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in 6-MWT Distance According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in 6-MWT Distance According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in 6-minute Walking Test (6-MWT) Distance According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in Systolic Blood Pressure (SBP) (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in Diastolic Blood Pressure (DBP) (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in Pro-B-type Natriuretic Peptide (BNP) Levels According to the Genetic Polymorphism of Beta-1 Adrenergic Receptor-CG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
measure: Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT
timeFrame: Baseline and Week 26 (or EOT)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St. Mary's Hospital, 505, Banpodong, SeoChoGu
Study officials:
affiliation: Merck Ltd.
name: Medical Responsible
role: STUDY_DIRECTOR
References: