Clinical trial NCT04448899: Ivabradine in Patients With Congestive Heart Failure
Official title: Effects of Ivabradine on Neopterin and NT-Pro BNP in Patients With Congestive Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Congestive Heart Failure
Lead sponsor: Damanhour University
Sponsor class: OTHER
First posted: 2020-06-26
Enrollment: 60
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: NT-Pro BNP
timeFrame: three months
measure: Neopterin
timeFrame: three months
Secondary outcomes:
measure: Heart Rate
timeFrame: Three Months
Other outcomes:
Locations:
city: Tanta
country: Egypt
facility: Tanta University Hospital
state: El-Gharbia
Study officials:
affiliation: Damanhour University, Faculty of Pharmacy
name: Rehab Werida, Lecturer
role: STUDY_DIRECTOR
affiliation: Alexandria University
name: Jayda M Dogheim, B. Pharm
role: PRINCIPAL_INVESTIGATOR
References:
citation: Komajda M, Tavazzi L, Francq BG, Bohm M, Borer JS, Ford I, Swedberg K; SHIFT Investigators. Efficacy and safety of ivabradine in patients with chronic systolic heart failure and diabetes: an analysis from the SHIFT trial. Eur J Heart Fail. 2015 Dec;17(12):1294-301. doi: 10.1002/ejhf.347. Epub 2015 Sep 16.
citation: Tavazzi L, Swedberg K, Komajda M, Bohm M, Borer JS, Lainscak M, Ford I; SHIFT Investigators. Efficacy and safety of ivabradine in chronic heart failure across the age spectrum: insights from the SHIFT study. Eur J Heart Fail. 2013 Nov;15(11):1296-303. doi: 10.1093/eurjhf/hft102. Epub 2013 Jun 26.
citation: Sasaki T, Takeishi Y, Suzuki S, Niizeki T, Kitahara T, Katoh S, Ishino M, Shishido T, Watanabe T, Kubota I. High serum level of neopterin is a risk factor of patients with heart failure. Int J Cardiol. 2010 Nov 19;145(2):318. doi: 10.1016/j.ijcard.2009.11.042. Epub 2010 Jan 6.
citation: Richards M, Troughton RW. NT-proBNP in heart failure: therapy decisions and monitoring. Eur J Heart Fail. 2004 Mar 15;6(3):351-4. doi: 10.1016/j.ejheart.2004.01.003.