Ivabradine in Patients With Congestive Heart Failure

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to assess the efficacy of Ivabradine therapy in patients with congestive heart failure using the cardiac biomarkers NT-Pro BNP and Neopterin.

Detailed Description
-----------------
Approval will be obtained from Research Ethics Committee of Faculty of Pharmacy, Damanhour University All participants have agreed to take part in this clinical study and provide informed consent A 3 months, prospective interventional study. Sixty ambulatory, clinically stable symptomatic patients with systolic chronic HF (≥ 4 weeks), on optimized standard medical therapy were consecutively included and randomly allocated to the ivabradine group (n=30) and non-ivabradine group (n=30). The baseline evaluation comprised physical examination, NYHA class, 12-lead electrocardi¬ography (ECG), Echocardiography, blood sampling for laboratory measurements, including NT-Pro BNP and Neopterin. Patients in the Ivabradine group were administered Ivabradine 5 mg twice daily and doses (2.5, 5, 7.5 mg) were to be adjusted upwards or downwards at every visit according to HR at rest and tolerability. Patients were followed up after 1 week of initiation of ivabradine therapy then monthly till the end of the study. Peripheral venous blood samples were drawn between 8 and 9 am after a 30-min rest in the supine position. Serum samples were frozen at -80°C until assay. Levels of NT-Pro BNP and Neopterin were detected using ELISA kits as prescribed by manufacturer. Statistical tests appropriate to the study will be conducted to evaluate significance of results Results, conclusion, discussion and recommendations will be given

Official Title
-----------------
Effects of Ivabradine on Neopterin and NT-Pro BNP in Patients With Congestive Heart Failure

Conditions
-----------------
Congestive Heart Failure

Intervention / Treatment
-----------------
* Drug: Ivabradine Oral Tablet
* Drug: Blacebo plus standard treatment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with chronic HF, on optimized medical therapy according to European Society of Cardiol¬ogy guidelines, with LV ejection fraction (LVEF) < 35% according to the Simpson method, New York Heart Association (NYHA) class II-III, and sinus rhythm and resting HR > 70/min were eligible for inclusion in the study. Exclusion Criteria: acute decompen¬sation (acute coronary syndromes and acute HF); hemodynamically significant valve disease; cer¬ebrovascular events during the previous 6 months; dysfunctional prosthetic heart valve; obstructive or non-obstructive cardiomyopathy; uncorrected congenital heart disease; active myocarditis; a his¬tory of resuscitation from sudden death; an absence of stable sinus rhythm, severe arrhythmias; HR < 60 bpm; sick sinus syndrome; second-degree and third-degree atrioventricular block; severe obesity (body mass index > 36 kg/m²); established or sus¬pected pulmonary diseases (vital capacity < 80% or forced expiratory volume in 1 s < 80% of age spe¬cific and sex-specific reference values); hemoglobin ≤ 11 g/dL; treatment with non-dihydropyridine calcium-channel blockers, class I antiarrhythmic agents, strong inhibitors of cytochrome P450-3A4, or QT interval-prolonging medications; acute and chronic kidney failure; pregnancy; hypo- and hy¬perthyroidism or acute infections.

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ivabradine<br>Patients administered Ivabradine 5 mg twice daily and doses (2.5, 5, 7.5 mg) were to be adjusted upwards or downwards at every visit according to HR at rest and tolerability. Patients were followed up after 1 week of initiation of ivabradine therapy then monthly till the end of the study. | Drug: Ivabradine Oral Tablet<br>* Ivabradine 5 mg twice daily and doses (2.5, 5, 7.5 mg) were to be adjusted upwards or downwards at every visit according to HR at rest and tolerability plus their standard treatment.<br>* Other names: Procoralan 5 mg film-coated tablets;|
| Placebo Comparator: Control<br>Patients administered a placebo twice daily. Patients were followed up after 1 week of initiation of the study then monthly till the end of the study. | Drug: Blacebo plus standard treatment<br>* Blacebo plus standard treatment<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NT-Pro BNP | Serum BNP (pg/ml) | three months | 
| Neopterin | Serum Neopterin (nmol/L) | three months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart Rate | Heart Rate (Beat/Minute) | Three Months |