A Prospective, Open-labeled, Multi-centric Trial in Subjects With Systolic Heart Failure to Evaluate Bisoprolol Treatment for the Effects on Surrogate Markers of Heart Failure in Korea (PRISM)
Heart Failure, Congestive
Drug: Low Dose Bisoprolol
Drug: High Dose Bisoprolol
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Prospective, Open-labeled Trial in Patients With Systolic Heart Failure to Evaluate Bisoprolol Treatment for the Effects on Surrogate Markers of Heart Failure in Korea (PRISM)|
- Percent Change From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]B-type natriuretic peptide (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. The percent change of NT-pro BNP was calculated according to the formula: N-terminal pro B-type natriuretic peptide (NT-proBNP) reduction ratio = 100*(Baseline NT-proBNP - Week 26 NT-proBNP)/Baseline NT-proBNP.
- Percentage of Participants Classified as Class I to IV According to New York Heart Association (NYHA) [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]New York Heart Association (NYHA) classification of heart failure: Class I: No limitation: ordinary physical exercise does not cause undue fatigue, dyspnea, or palpitations. Class II: Slight limitation of physical activity: comfortable at rest but ordinary activity results in fatigue, palpitations, or dyspnea. Class III: Marked limitation of physical activity: comfortable at rest but less than ordinary activity results in symptoms. Class IV: Unable to carry out any physical activity without discomfort: symptoms of heart failure are present even at rest with increased discomfort with any physical activity.
- Change From Baseline in 6-minute Walking Test (6-MWT) Distance at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]6-minute Walking Test (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 Echocardiographic Left Ventricular Ejection Fraction (LVEF) at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]LVEF was defined as the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat and it is used to measure the cardiac output for the heart.
- Change From Baseline in Echocardiographic Left Ventricular Size at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]Left ventricle size was measured as systolic and diastolic Left Ventricular Internal Dimension (LVID). Diastolic dimension was measured of the left ventricle at the level of the chordae tendineae. The systolic dimension was measured as the smallest dimension between the left septal endocardium and the posterior wall endocardium during systole, whether or not the two walls were exactly apposed.
- Number of Participants Who Were Re-hospitalized Due to Heart Failure and Who Died Due to Cardiovascular Disorder [ Time Frame: Baseline up to Week 26 ] [ Designated as safety issue: No ]
- Number of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to Week 26 ] [ Designated as safety issue: Yes ]An adverse event (AE) is defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
- Mean Change From Baseline in Global Assessment of Congestive Heart Failure (CHF) Score at Week 26 [ Time Frame: Baseline and Week 26 ] [ Designated as safety issue: No ]Global assessment of CHF: The Investigator defined, graded, and recorded the participant's symptoms and signs by using a 6-point CHF scale ranging from 0 (unassessable), 1 (worsened), 2 (no change), 3 (mildly improved), 4 (moderately improved) and 5 (markedly improved).
|Study Start Date:||October 2009|
|Study Completion Date:||August 2012|
|Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
|Experimental: Low Dose Bisoprolol||
Drug: Low Dose Bisoprolol
Bisoprolol tablet (Concor) will be administered orally at a starting dose of 1.25 milligram (mg) once daily for 2 weeks. The dose will be further escalated from 1.25 mg to 2.5 mg once daily after 2 weeks and will be administered up to 26 weeks, only if the previous administered dose is well tolerated. If the subject could not tolerate the increased dose, then the last tolerated dose will be maintained up to 26 weeks.
Other Name: Concor
|Experimental: High Dose Bisoprolol||
Drug: High Dose Bisoprolol
Bisoprolol tablet (Concor) will be administered orally at a starting dose of 3.75 mg once daily for 2 weeks. The dose will be subsequently increased to 5 mg, 7.5 mg, or 10 mg once daily every two weeks and will be administered up to 26 weeks, only if the previous administered dose is well tolerated. If the subject could not tolerate the increased dose, then the last tolerated dose will be maintained up to 26 weeks.
Other Name: Concor
Subjects with systolic congestive heart failure (CHF) will be enrolled in this study after proper evaluation of NT-proBNP, global assessment of CHF, 6-minute walking test and improvement score of New York Heart Association (NYHA) and echocardiogram (left ventricular chamber size and ejection fraction [LVEF]). Each subject will be orally administered bisoprolol for 6 months starting at 1.25 mg at the Week 0 and titrated up to 10 mg during the 6 month period if the persistent standing systolic blood pressure (SBP) is greater than (>) 90 millimeter of mercury (mm Hg) and there is no symptom of hypotension at the current dose medication (syncope, loss of consciousness, dizziness when standing up).
• To evaluate the effect of bisoprolol (between low dose and high dose) on surrogate markers of heart failure in Korea
To evaluate bisoprolol for the effects on clinical improvement of heart failure in Korea:
- New York Heart Association (NYHA),
- 6-minutes walking test
- Echocardiogram (left ventricular chamber size and LVEF)
- Hospitalization due to heart failure
- To evaluate the safety and tolerability of bisoprolol
- Global assessment of CHF
Please refer to this study by its ClinicalTrials.gov identifier: NCT01074307
|Korea, Republic of|
|Konkuk University Medical Center|
|Seoul, Korea, Republic of|
|Study Director:||Medical Responsible||Merck Ltd.|