Early Use of Ivabradine in Heart Failure (Ivabradine)

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

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.

Study Overview

• Status: Unknown
• Conditions: Decompensated Heart Failure; Heart Failure With Reduced Ejection Fraction
• Intervention / Treatment: Drug: Ivabradine; Drug: Bisoprolol

Detailed Description

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:

1. Physical examination (heart rate, blood pressure, dyspnea and orthopnea symptoms)
2. NYHA class
3. Pro-NT-BNP serum level, ST2 serum level
4. Echocardiography (left ventricular ejection fraction)
5. Score of Minnesota Living with Heart Failure Questionnaire these objectives will be measured baseline, 2 weeks and after 3 months

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • El demerdash hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient with acute heart failure either newly diagnosed or decompensated heart failure after stabilization
2. Patients > 18 years old
3. Left ventricular ejection fraction less than 40 % of presumed irreversible etiology
4. Clinically stable 24-48 hours after admission
5. Sinus rhythm with heart rate above 70 bpm
6. No previous treatment with ivabradine

Exclusion Criteria:

1. Patients less than 18 years.
2. Arterial fibrillation before inclusion.
3. 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ivabradine group; 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; Ivabradine is pacemaker current I(f) inhibitor thereby slowing heart rates without exhibiting negative inotropic effect on the myocardium or altering ventricular action potential; Other Names: Procoralan; Drug: Bisoprolol; Bisoprolol is beta-blocker; Other Names: concor
Active Comparator: Control group; 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; Ivabradine is pacemaker current I(f) inhibitor thereby slowing heart rates without exhibiting negative inotropic effect on the myocardium or altering ventricular action potential; Other Names: Procoralan; Drug: Bisoprolol; Bisoprolol is beta-blocker; Other Names: concor

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ain Shams University
• Collaborators: Sadat City University

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2018
• Primary Completion (Anticipated): December 23, 2019
• Study Completion (Anticipated): December 23, 2019

Study Registration Dates

• First Submitted: October 8, 2018
• First Submitted That Met QC Criteria: October 9, 2018
• First Posted (Actual): October 10, 2018

Study Record Updates

• Last Update Posted (Actual): October 11, 2018
• Last Update Submitted That Met QC Criteria: October 9, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Ivabradine; Decompensated Heart Failure; ST2 Biomarker
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Bisoprolol
• Other Study ID Numbers: ClinicalPH110

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No