A Study of Ivabradine in African-American/ Black Subjects With Heart Failure and Left Ventricular Systolic Dysfunction.
Condition: Heart Failure (HF)
MeSH terms: Heart Failure; Ventricular Dysfunction, Left
Intervention: Ivabradine
Intervention description: Film-coated tablets taken orally with food twice a day. Tablets supplied in strengths of 5.0 mg and 7.5 mg. 5.0 tablets were split into equal halves for dosages of 2.5 mg.
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Cardiac; Congestive; Decompensation; Heart Failure; Left-Sided; Myocardial; Corlanor; Ivabradine; African American; Black; Michigan

Summary:

      This study is a prospective, open-label, single-arm intervention study in
      African-American/Black subjects with heart failure and reduced ejection fraction (HFrEF).

      There will be a 7-day screening period, a 57-day open-label treatment period, and a safety
      follow-up at day 87 or 30 days after the last administration of the investigational product.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject has provided informed consent/assent prior to initiation of any study specific
             activities/ procedures

          -  Male or female subject ≥ 18 years of age, describing self as African American/Black

          -  Must have a diagnosis of heart failure (HF) confirmed by medical records, be in stable
             condition, and treated with stable optimal pharmacological therapy as per their
             personal physician's care.

          -  Left ventricular ejection fraction (LVEF) ≤ 35% confirmed by investigator

          -  New York Heart Association (NYHA) class II to IV assessed at the time of screening

          -  Electrocardiogram (ECG) documentation at the time of screening of sinus rhythm with
             resting heart rate (HR) ≥ 70 bpm by local ECG reading

          -  Must be able to complete a 6-minute walk test (6MWT) and wear an accelerometer

        Exclusion Criteria:

          -  Recent myocardial infarction (≤ 2 months) or stroke (≤ 1 month) prior to enrollment

          -  If the subject received within 3 months before or is scheduled to receive within 42
             days after enrollment any of the following: revascularization, ventricular assist
             device, continuous or intermittent inotropic therapy, hospice care, major organ
             transplant, or is receiving renal replacement therapy by dialysis

          -  If the subject received implantation of a cardioverter defibrillator or cardiac
             resynchronization therapy within 42 days before or is scheduled to receive
             implantation of a cardioverter defibrillator or cardiac resynchronization therapy
             within 42 days after enrollment

          -  Severe primary valve disease or scheduled for surgery for valvular heart disease

          -  Pacemaker with atrial or ventricular pacing (except bi-ventricular pacing) >40% of the
             time, or with a stimulation threshold at the atrial or ventricular level ≥ 60 bpm

          -  Permanent atrial fibrillation or flutter

          -  Sick sinus syndrome, sinoatrial block, or second and third degree atrio-ventricular
             block

          -  History of symptomatic or sustained (≥ 30 sec) ventricular arrhythmia unless a
             cardioverter defibrillator was implanted

          -  History of congenital QT syndrome

          -  Any cardioverter defibrillator shock experienced within 1 month of enrollment

          -  Hypertrophic obstructive cardiomyopathy, active myocarditis or constrictive
             pericarditis, or clinically significant congenital heart disease

          -  Chronic antiarrhythmic therapy (except digitalis)

          -  Scheduled outpatient intravenous (IV) infusions for HF (eg, inotropes,vasodilators
             [eg, nesiritide], diuretics) or routinely scheduled ultrafiltration

          -  Evidence of digitalis intoxication within 7 days prior to screening

          -  Systolic blood pressure > 180 mm Hg or < 90 mm Hg, or diastolic blood pressure > 110
             mm Hg or < 50 mm Hg at any time during the screening phase

          -  Known untreated hypothyroidism or hyperthyroidism, adrenal insufficiency, active
             vasculitis due to collagen vascular disease

          -  Have known acute or serious co-morbid condition (e.g, major infection or hematologic,
             renal, hepatic, metabolic, gastrointestinal or endocrine dysfunction) that may
             interfere with the study, or severe concomitant non-cardiovascular disease that is
             expected to reduce life expectancy to less than 1 year or malignancy within 5 years
             prior to enrollment with the following exceptions: localized basal or squamous cell
             carcinoma of the skin or cervical intraepithelial neoplasia

          -  Subjects taking QT prolonging medicinal products for cardiovascular (e.g, but not
             limited to, quinidine, disopyramide, bepridil, sotalol, ibutilide, amiodarone) or
             non-cardiovascular disease (e.g, but not limited to, pimozide, ziprasidone,
             sertindole, mefloquine, halofantrine, pentamidine, cisapride, IV erythromycin).

          -  Subjects exposed to a strong CYP3A4 inhibitor (examples of strong CYP3A4 inhibitors
             include; azole antifungals [eg, itraconazole], macrolide antibiotics [e.g,
             clarithromycin, telithromycin], human immunodeficiency virus (HIV) protease
             inhibitors, [eg, nelfinavir], and nefazodone]) within 14 days prior to enrollment, or
             to a strong CYP3A4 inducer (examples of CYP3A4 inducers include; St. John's wort,
             rifampicin, barbiturates, and phenytoin) within 28 days prior to enrollment

          -  Subjects who received diltiazem or verapamil within 48 hours prior to enrollment.

          -  Previously received ivabradine prior to participation in this study

          -  Currently receiving treatment in another investigational device or drug study, or less
             than 30 days since ending treatment on another investigational device or drug
             study(ies). Other investigational procedures while participating in this study are
             excluded.

          -  Female subject is pregnant or breastfeeding or planning to become pregnant or
             breastfeed during treatment and for an additional 14 days after the last dose of
             investigational product. Females of childbearing potential should only be included in
             the study after a confirmed menstrual period and a negative highly sensitive urine
             pregnancy test.

          -  Female subjects of childbearing potential unwilling to use 1 highly effective method
             of contraception during treatment and for an additional 14 days after the last dose of
             investigational product.

          -  Subject has known sensitivity to any of the products or components to be administered
             during dosing.

          -  Subject likely not to be available to complete all protocol required study visits or
             procedures, and/or to comply with all required study procedures to the best of the
             subject and investigator's knowledge.

          -  History or evidence of any other clinically significant disorder, condition or disease
             (with the exception of those outlined above) that, in the opinion of the investigator
             or Amgen physician, if consulted, would pose a risk to subject safety or interfere
             with the study evaluation, procedures or completion.