A Study of Ivabradine in African-American/ Black Subjects With Heart Failure and Left Ventricular Systolic Dysfunction.

NCT ID: NCT03456856

Last Updated: 2021-10-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-28
• Study Completion Date: 2019-05-20

Brief 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.

Detailed Description

The goal of this study is to determine the impact of adding ivabradine therapy to the standard of care (SOC) in African-American/Black subjects with Heart Failure (HF) and reduced ejection fraction (HFrEF) on changes in heart rate (HR) from baseline (SOC alone). Changes in HR from baseline will be correlated with the changes from baseline in activity level of the subjects, as measured by both a standard 6-minute walk distance and an accelerometer device.

The primary hypothesis is that ivabradine effectively reduces HR between baseline and day 57 in African-American/Black subjects. Because mean reductions of approximately 5 beat per minute (bpm) have been observed in the overall placebo-treated subjects in the SHIFT study as well as in the placebo-treated subjects of the subgroup analysis of non-African-American/Black subjects enrolled in the SHIFT study, we will test whether the mean reduction with ivabradine exceeds 5 bpm, and estimate the degree to which the mean reduction with ivabradine exceeds 5 bpm.

Conditions

Heart Failure (HF)

Keywords

Cardiac; Congestive; Decompensation; Heart Failure; Left-Sided; Myocardial; Corlanor; Ivabradine; African American; Black; Michigan

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ivabradine

The starting dose of ivabradine was 5 mg twice daily (BID), although investigators had the discretion to start participants at 2.5 mg BID if participant had a history of conduction defects, or bradycardia that could lead to hemodynamic compromise. Dose was adjusted at Day 15 (and at any other clinical visit) between 2.5 - 7.5 mg BID based on heart rate and signs/symptoms of bradycardia.

Group Type: EXPERIMENTAL

Ivabradine

Intervention Type: DRUG

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.

Interventions

Ivabradine

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.

Intervention Type: DRUG

Other Intervention Names

Corlanor®

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Research Site

Wilmington, Delaware, United States

Research Site

Detroit, Michigan, United States

Research Site

Buffalo, New York, United States

Countries

United States

References

Lanfear DE, Neaton KR, Lu C, Liu Y, Dent-Acosta RE. A Phase 4, Open-Label, Single-Arm Study Assessing the Efficacy and Safety of Ivabradine in African American Patients with Heart Failure and Reduced Ejection Fraction. Cardiol Ther. 2020 Dec;9(2):561-568. doi: 10.1007/s40119-020-00196-1. Epub 2020 Aug 17.

Reference Type: BACKGROUND

PMID: 32808163 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

20160231

Identifier Type: -

Identifier Source: org_study_id