Early Use of Ivabradine in Heart Failure

Study Overview
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Brief Summary
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The aim of the work is to Evaluate the efficacy, quality of life and safety of early addition of ivabradine to B-blocker in reduced EF heart failure patients after acute decompensation compared to the standard treatment.

Detailed Description
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this study is a Prospective randomized open label study will be conducted on Egyptian patient with heart failure with reduced ejection fraction(rEF HF). Each of the eligible patients will be randomized to one of these groups, early administration of Ivabradine and B-blocker group or control group which follows American Heart Association treatment guidelines of rEF HF. The objectives include the following: Physical examination (heart rate, blood pressure, dyspnea and orthopnea symptoms) NYHA class Pro-NT-BNP serum level, ST2 serum level Echocardiography (left ventricular ejection fraction) Score of Minnesota Living with Heart Failure Questionnaire these objectives will be measured baseline, 2 weeks and after 3 months

Official Title
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The Impact of Ivabradine Administration on Clinical Outcome and Biomarkers of Decompensated Heart Failure

Conditions
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Heart Failure With Reduced Ejection Fraction, Decompensated Heart Failure

Intervention / Treatment
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* Drug: Ivabradine
* Drug: Bisoprolol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with acute heart failure either newly diagnosed or decompensated heart failure after stabilization Patients > 18 years old Left ventricular ejection fraction less than 40 % of presumed irreversible etiology Clinically stable 24-48 hours after admission Sinus rhythm with heart rate above 70 bpm No previous treatment with ivabradine Exclusion Criteria: Patients less than 18 years. Arterial fibrillation before inclusion. Ventricular dysfunction due to acute event (Myocarditis, AMI). 4- cardiogenic shock 5. Patients are taking drug interact with ivabradine. 6- carrier or candidate for pacemaker, heart transportation, cardiac surgery or other cardiovascular procedure

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ivabradine group<br>an initial dose of 5 mg/12 hours of Ivabradine will be added to beta-blockers (bisoprolol 2.5 mg/day) and ivabradine will be increased until a dose of 7.5 mg/12 hours according to HR. The heart rate target will be at least <70 bpm and not lower than 60 bpm. If HR decreases below 60 bpm, ivabradine and/or beta-blockers doses will be decreased to the previous dose. After discharge, beta-blockers up-titration will be continued during follow-up visit. | Drug: Ivabradine<br>* Ivabradine is pacemaker current I(f) inhibitor thereby slowing heart rates without exhibiting negative inotropic effect on the myocardium or altering ventricular action potential<br>* Other names: Procoralan;Drug: Bisoprolol<br>* Bisoprolol is beta-blocker<br>* Other names: concor;|
| Active Comparator: Control group<br>beta-blocker (bisoprolol 2.5 mg/day) and it will be doubled every 2 weeks during the admission according to the stability of HR, blood pressure and tolerability of patients. Ivabradine will be only added after reaching bisoprolol optimal dose (10mg) or maximum tolerated dose and the HR is still above 70 bpm. If HR decreases below 60 bpm, ivabradine dose will be decreased. | Drug: Ivabradine<br>* Ivabradine is pacemaker current I(f) inhibitor thereby slowing heart rates without exhibiting negative inotropic effect on the myocardium or altering ventricular action potential<br>* Other names: Procoralan;Drug: Bisoprolol<br>* Bisoprolol is beta-blocker<br>* Other names: concor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum Pro-BNP level | Elevated NT-proBNP parallel HF disease severity and it is suggestive of worse clinical outcomes and mortality in HF | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ST2 serum level | Repeated ST2 measurements appeared to be a strong predictor of outcome especially in patients with acute HF. Also, ST2 levels in patients with acute HF are significantly higher than in patients with chronic HF and fall rapidly over days to weeks during HF treatment. This lack of reduction in ST2 level during acute HF treatment is predictive of mortality. So, persistently high levels of ST2 were associated with increased mortality risk | 3 months | 
| The effect on patient quality of life using Minnesota Living with Heart Failure Questionnaire | The questionnaire is comprised of 21 important physical, emotional and socioeconomic ways heart failure can adversely affect a patient's life. the patient marks a 0 (zero) to 5 scale to indicate how much each itemized adverse of heart failure has prevented the patient from living as he or she wanted to live during the past 4 weeks. it is simply scored by summation of all 21 responses.The simple sum of the responses that ranges from 0 to 105 is a measurement of heart failure severity as indicated by its adverse effect on the respondent's life during the past month | 3 months of follow-up. | 
| NYHA class assessment | This classification provides a simple way of classifying the extent of heart failure. It classifies patients in one of four categories based on their limitations during physical activity; the limitations/symptoms are in regard to normal breathing and varying degrees in shortness of breath | 3 months | 
| Heart rate | Measuring heart rate | 3 months | 
| Left ventricular ejection fraction assessment | Two-dimensional echocardiogram coupled with Doppler flow studies will be performed | 3 months | 
| Blood pressure | Measuring systolic and diastolic blood pressure | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Decompensated Heart Failure, Ivabradine, ST2 Biomarker