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

Chronic Heart Failure Clinical Trial

— ABBA  

Official title:

Association Between Beta-1 and Beta-2 Adrenergic Receptor Polymorphism and Beta-blocker (Bisoprolol) Therapy in Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01104558
• Other study ID #: EMD084000-500
• Status: Completed
• Phase: Phase 4
• First received: February 24, 2010
• Last updated: January 20, 2014
• Start date: December 2008
• Est. completion date: July 2010

Study information

• Verified date: January 2014
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: July 2010
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Heart Failure
• Heart Failure

Intervention

Drug:
• Bisoprolol
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.

Locations

Country	Name	City	State
Korea, Republic of	The Catholic University of Korea Seoul St. Mary's Hospital, 505, Banpodong, SeoChoGu	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Merck KGaA	Merck Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)		Baseline and Week 26 (or EOT)	No
Primary	Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT		Baseline and Week 26 (or EOT)	No
Primary	Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT		Baseline and Week 26 (or EOT)	No
Primary	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		Baseline and Week 26 (or EOT)	No
Secondary	Number of Participants With Hospitalization Due to Heart Failure		Baseline to Week 26 (or EOT)	No
Secondary	Duration of Hospitalization Due to Heart Failure		Baseline to Week 26 (or EOT)	No
Secondary	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	6 MWT distance was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.	Baseline and Week 26 (or EOT)	No
Secondary	Change From Baseline in 6-MWT Distance According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT	6 MWT distance was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.	Baseline and Week 26 (or EOT)	No
Secondary	Change From Baseline in 6-MWT Distance According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT	6 MWT distance was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.	Baseline and Week 26 (or EOT)	No
Secondary	Change From Baseline in 6-minute Walking Test (6-MWT) Distance According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT	6 MWT distance was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed.	Baseline and Week 26 (or EOT)	No
Secondary	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	The change in heart rate was calculated as 6-MWT before walking heart rate at Week 26 minus 6-MWT before walking heart rate at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	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	The change in heart rate was calculated as 6-MWT before walking heart rate at Week 26 minus 6-MWT before walking heart rate at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	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	The change in heart rate was calculated as 6-MWT before walking heart rate at Week 26 minus 6-MWT before walking heart rate at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT	The change in heart rate was calculated as 6-MWT before walking heart rate at Week 26 minus 6-MWT before walking heart rate at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	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	The change in heart rate was calculated as 6-MWT after walking heart rate at Week 26 minus 6-MWT after walking heart rate at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	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	The change in heart rate was calculated as 6-MWT after walking heart rate at Week 26 minus 6-MWT after walking heart rate at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	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	The change in heart rate was calculated as 6-MWT after walking heart rate at Week 26 minus 6-MWT after walking heart rate at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT	The change in heart rate was calculated as 6-MWT after walking heart rate at Week 26 minus 6-MWT after walking heart rate at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	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	The change in SBP was calculated as 6-MWT before walking SBP at Week 26 minus 6-MWT before walking SBP at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	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	The change in SBP was calculated as 6-MWT before walking SBP at Week 26 minus 6-MWT before walking SBP at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	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	The change in SBP was calculated as 6-MWT before walking SBP at Week 26 minus 6-MWT before walking SBP at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT	The change in SBP was calculated as 6-MWT before walking SBP at Week 26 minus 6-MWT before walking SBP at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	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	The change in SBP was calculated as 6-MWT after walking SBP at Week 26 minus 6-MWT after walking SBP at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	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	The change in SBP was calculated as 6-MWT after walking SBP at Week 26 minus 6-MWT after walking SBP at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	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	The change in SBP was calculated as 6-MWT after walking SBP at Week 26 minus 6-MWT after walking SBP at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT	The change in SBP was calculated as 6-MWT after walking SBP at Week 26 minus 6-MWT after walking SBP at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	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	The change in DBP was calculated as 6-MWT before walking DBP at Week 26 minus 6-MWT before walking DBP at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	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	The change in DBP was calculated as 6-MWT before walking DBP at Week 26 minus 6-MWT before walking DBP at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	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	The change in DBP was calculated as 6-MWT before walking DBP at Week 26 minus 6-MWT before walking DBP at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT	The change in DBP was calculated as 6-MWT before walking DBP at Week 26 minus 6-MWT before walking DBP at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	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	The change in DBP was calculated as 6-MWT after walking DBP at Week 26 minus 6-MWT after walking DBP at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	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	The change in DBP was calculated as 6-MWT after walking DBP at Week 26 minus 6-MWT after walking DBP at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	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	The change in DBP was calculated as 6-MWT after walking DBP at Week 26 minus 6-MWT after walking DBP at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT	The change in DBP was calculated as 6-MWT after walking DBP at Week 26 minus 6-MWT after walking DBP at baseline.	Baseline and Week 26 (or EOT)	No
Secondary	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	BNP is a substance secreted from the ventricles or lower chambers of the heart in response to changes in pressure that occur when heart failure develops and worsens. The level of BNP in the blood increases when heart failure symptoms worsen, and decreases when the heart failure condition is stable. The BNP level in a person with heart failure is higher than in a person with normal heart function.	Baseline and Week 26 (or EOT)	No
Secondary	Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT	BNP is a substance secreted from the ventricles or lower chambers of the heart in response to changes in pressure that occur when heart failure develops and worsens. The level of BNP in the blood increases when heart failure symptoms worsen, and decreases when the heart failure condition is stable. The BNP level in a person with heart failure is higher than in a person with normal heart function.	Baseline and Week 26 (or EOT)	No
Secondary	Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT	BNP is a substance secreted from the ventricles or lower chambers of the heart in response to changes in pressure that occur when heart failure develops and worsens. The level of BNP in the blood increases when heart failure symptoms worsen, and decreases when the heart failure condition is stable. The BNP level in a person with heart failure is higher than in a person with normal heart function.	Baseline and Week 26 (or EOT)	No
Secondary	Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT	BNP is a substance secreted from the ventricles or lower chambers of the heart in response to changes in pressure that occur when heart failure develops and worsens. The level of BNP in the blood increases when heart failure symptoms worsen, and decreases when the heart failure condition is stable. The BNP level in a person with heart failure is higher than in a person with normal heart function.	Baseline and Week 26 (or EOT)	No