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

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ClinicalTrials.gov Identifier: NCT03456856
Recruitment Status : Recruiting
First Posted : March 7, 2018
Last Update Posted : October 26, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:

This study is a prospective, open-label, single-arm intervention study in African-American/Black subjects with 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.


Condition or disease Intervention/treatment Phase
Heart Failure (HF) Drug: 5mg Ivabradine Phase 4

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 genetic background of a subset of subjects with available genetic data in the studied population, as well as 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-label, Single-arm, Study Assessing the Efficacy and Safety of Ivabradine (Corlanor) in African-American/Black Subjects With Heart Failure and Left Ventricular Systolic Dysfunction
Actual Study Start Date : September 28, 2017
Estimated Primary Completion Date : March 11, 2019
Estimated Study Completion Date : March 11, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Ivabradine

Arm Intervention/treatment
Experimental: Initial Dose: 5 mg BID

5mg Ivabradine: On day 1, eligible subjects with confirmed sinus rhythm and HR ≥ 70 bpm will be enrolled into a 57-day open-label treatment period. The starting dose of ivabradine is 5 mg twice daily (BID).

2.5mg Ivabradine: In subjects with a history of conduction defects, or in subjects in whom bradycardia could lead to hemodynamic compromise, therapy is to be initiated at 2.5 mg BID.

Changes in HR from baseline will be correlated with the genetic background of the studied population, as well as 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.

Drug: 5mg Ivabradine

On day 15, the 5mg dose will be titrated according to HR :

HR ≥ 60 bpm 7.5 mg BID HR ≥ 50 bpm, < 60 bpm 5.0 mg BID HR < 50 bpm and/or signs or symptoms of bradycardia 2.5 mg BID

Ivabradine dose levels can be adapted to HR at any clinical visit if necessary.

Other Name: Corlanor




Primary Outcome Measures :
  1. Change in HR from baseline to day 57 [ Time Frame: 57 days ]
    Determine whether ivabradine effectively reduces HR from baselineto day 57 in African-American/Black subjects.



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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 HF confirmed by medical records, be in stable condition, and treated with stable optimal pharmacological therapy as per their personal physician's care.
  • LVEF ≤ 35% confirmed by investigator
  • NYHA class II to IV assessed at the time of screening
  • Electrocardiogram (ECG) documentation at the time of screening of sinus rhythm with resting HR ≥ 70 bpm by local ECG reading
  • Must be able to complete a 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 (eg, 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 (eg, but not limited to, quinidine, disopyramide, bepridil, sotalol, ibutilide, amiodarone) or non-cardiovascular disease (eg, 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 [eg, 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. Refer to Appendix 5 for additional contraceptive information.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03456856


Contacts
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

Locations
United States, Delaware
Research Site Recruiting
Wilmington, Delaware, United States, 19803
United States, Michigan
Research Site Recruiting
Detroit, Michigan, United States, 48202
United States, New York
Research Site Recruiting
Buffalo, New York, United States, 14215
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen

Additional Information:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03456856     History of Changes
Other Study ID Numbers: 20160231
First Posted: March 7, 2018    Key Record Dates
Last Update Posted: October 26, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
URL: https://www.amgen.com/datasharing

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Amgen:
Cardiac
Congestive
Decompensation
Heart Failure
Left-Sided
Myocardial
Corlanor
Ivabradine
African American
Black
Michigan

Additional relevant MeSH terms:
Heart Failure
Ventricular Dysfunction, Left
Heart Diseases
Cardiovascular Diseases
Ventricular Dysfunction