Phase 4 N=100 Treatment

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

Chronic Heart Failure

Bottom Line

View on ClinicalTrials.gov: NCT01104558 ↗

Enrolled (actual)

100

Serious AEs

7.0%

Results posted

Apr 2012

Primary outcome: 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) — 32.44; 32.89; 32.20; -8.44 Percent LVEF

Study Design & Population

Study type: Interventional
Phase: Phase 4
Interventions: Bisoprolol (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Merck KGaA, Darmstadt, Germany
Primary completion: Jul 2010

Outcome Measures

Outcome	Result	p-value
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)	32.44; 32.89; 32.20; -8.44; -9.36; -9.20	—
PRIMARY Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT	31.31; 32.67; 33.03; -9.39; -7.87; -9.76	—
PRIMARY Change From Baseline in Echocardiographic LVEF According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT	38.00; 33.01; 32.38; -13.00; -8.71; -8.71	—
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	32.37; 33.14; 29.87; -7.69; -10.19; -12.47	—
SECONDARY Number of Participants With Hospitalization Due to Heart Failure	1	—
SECONDARY Duration of Hospitalization Due to Heart Failure	41	—
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	401.36; 381.71; 371.70; -20.85; -0.90; -20.10	—
SECONDARY Change From Baseline in 6-MWT Distance According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT	449.43; 414.73; 333.19; 0.46; -12.18; -27.20	—
SECONDARY Change From Baseline in 6-MWT Distance According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT	468.00; 404.63; 390.22; -57.00; 12.23; -20.51	—
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	390.68; 395.11; 431.67; -13.86; -17.61; -6.67	—
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	76.47; 82.25; 83.20; 8.91; 11.79; 12.00	—
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	79.21; 79.02; 77.56; 13.21; 9.20; 9.37	—
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	92.00; 76.60; 78.82; 9.00; 10.33; 9.86	—
SECONDARY Change From Baseline in Heart Rate (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT	77.29; 80.80; 77.33; 10.92; 7.83; 15.00	—
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	92.02; 90.92; 92.80; 11.83; 15.88; 4.60	—
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	87.86; 95.05; 88.74; 11.21; 12.37; 13.59	—
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	90.00; 84.40; 93.44; -3.00; 9.73; 13.45	—
SECONDARY Change From Baseline in Heart Rate (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT	92.41; 89.30; 105.33; 14.59; 8.53; 20.00	—
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	121.81; 123.54; 117.40; -0.96; -2.75; -0.40	—
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	132.36; 117.83; 123.15; 2.50; -4.32; 0.92	—
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	130.00; 115.53; 123.43; -13.00; -4.33; -0.62	—
SECONDARY Change From Baseline in SBP (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT	118.92; 126.53; 127.33; -2.25; -1.13; 8.00	—
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	128.77; 130.25; 128.60; -2.92; -0.46; 5.40	—
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	138.71; 126.56; 128.23; 3.29; -4.34; -0.15	—
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	113.00; 124.47; 130.54; -18.00; -4.93; -0.68	—
SECONDARY Change From Baseline in SBP (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT	127.52; 131.27; 135.33; -2.10; -2.37; 12.00	—
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	75.69; 78.17; 79.40; 0.10; 0.29; 0.60	—
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	83.14; 75.59; 74.85; 4.07; -0.88; -0.23	—
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	68.00; 71.80; 77.91; -28.00; -1.93; 1.11	—
SECONDARY Change From Baseline in DBP (6 MWT- Before Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT	74.90; 78.87; 82.67; 0.06; -0.13; 5.33	—
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	80.15; 80.50; 81.80; -0.04; 3.63; 1.00	—
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	86.14; 79.66; 78.35; 4.21; -0.54; 2.04	—
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	65.00; 77.40; 81.28; -21.00; 0.87; 1.51	—
SECONDARY Change From Baseline in DBP (6 MWT- After Walking) According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT	79.10; 81.97; 84.33; 0.79; 1.27; 4.67	—
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	1484.02; 851.47; 1011.30; 292.10; 310.63; 394.32	—
SECONDARY Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-AG at Week 26 or EOT	2809.30; 823.71; 1139.07; 1600.88; -33.98; 137.68	—
SECONDARY Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of Beta-2 Adrenergic Receptor-CG at Week 26 or EOT	120.80; 878.31; 1368.67; 84.91; 131.60; 346.20	—
SECONDARY Change From Baseline in Pro-BNP Levels According to the Genetic Polymorphism of GRK5-AG at Week 26 or EOT	895.52; 1854.63; 1527.09; -33.78; 799.31; 861.39	—

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.

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01104558). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.