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

This study has been completed.
Sponsor:
Collaborator:
Merck Ltd.
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01104558
First received: February 24, 2010
Last updated: January 20, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Chronic Heart Failure
Drug: Bisoprolol
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Association Between Beta-1 and Beta-2 Adrenergic Receptor Polymorphism and Beta-blocker (Bisoprolol) Therapy in Heart Failure

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • 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) [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
  • Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
  • Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Participants With Hospitalization Due to Heart Failure [ Time Frame: Baseline to Week 26 (or EOT) ] [ Designated as safety issue: No ]
  • Duration of Hospitalization Due to Heart Failure [ Time Frame: Baseline to Week 26 (or EOT) ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in 6-MWT Distance According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in 6-MWT Distance According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in 6-minute Walking Test (6-MWT) Distance According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    The change in SBP was calculated as 6-MWT before walking SBP at Week 26 minus 6-MWT before walking SBP at baseline.

  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    The change in SBP was calculated as 6-MWT before walking SBP at Week 26 minus 6-MWT before walking SBP at baseline.

  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    The change in SBP was calculated as 6-MWT before walking SBP at Week 26 minus 6-MWT before walking SBP at baseline.

  • Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    The change in SBP was calculated as 6-MWT before walking SBP at Week 26 minus 6-MWT before walking SBP at baseline.

  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    The change in SBP was calculated as 6-MWT after walking SBP at Week 26 minus 6-MWT after walking SBP at baseline.

  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    The change in SBP was calculated as 6-MWT after walking SBP at Week 26 minus 6-MWT after walking SBP at baseline.

  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    The change in SBP was calculated as 6-MWT after walking SBP at Week 26 minus 6-MWT after walking SBP at baseline.

  • Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    The change in SBP was calculated as 6-MWT after walking SBP at Week 26 minus 6-MWT after walking SBP at baseline.

  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    The change in DBP was calculated as 6-MWT before walking DBP at Week 26 minus 6-MWT before walking DBP at baseline.

  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    The change in DBP was calculated as 6-MWT before walking DBP at Week 26 minus 6-MWT before walking DBP at baseline.

  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    The change in DBP was calculated as 6-MWT before walking DBP at Week 26 minus 6-MWT before walking DBP at baseline.

  • Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    The change in DBP was calculated as 6-MWT before walking DBP at Week 26 minus 6-MWT before walking DBP at baseline.

  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    The change in DBP was calculated as 6-MWT after walking DBP at Week 26 minus 6-MWT after walking DBP at baseline.

  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    The change in DBP was calculated as 6-MWT after walking DBP at Week 26 minus 6-MWT after walking DBP at baseline.

  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    The change in DBP was calculated as 6-MWT after walking DBP at Week 26 minus 6-MWT after walking DBP at baseline.

  • Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    The change in DBP was calculated as 6-MWT after walking DBP at Week 26 minus 6-MWT after walking DBP at baseline.

  • 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 [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT [ Time Frame: Baseline and Week 26 (or EOT) ] [ Designated as safety issue: No ]
    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.


Enrollment: 100
Study Start Date: December 2008
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    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.
    Other Name: Concor
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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01104558

Locations
Korea, Republic of
The Catholic University of Korea Seoul St. Mary's Hospital, 505, Banpodong, SeoChoGu
Seoul, Korea, Republic of
Sponsors and Collaborators
Merck KGaA
Merck Ltd.
Investigators
Study Director: Medical Responsible Merck Ltd.
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01104558     History of Changes
Other Study ID Numbers: EMD084000-500
Study First Received: February 24, 2010
Results First Received: March 13, 2012
Last Updated: January 20, 2014
Health Authority: Korea: Food and Drug Administration

Keywords provided by Merck KGaA:
Bisoprolol
Chronic Heart failure

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Adrenergic Agents
Bisoprolol
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists

ClinicalTrials.gov processed this record on July 24, 2014