Heart Failure (HF)Phase 4NCT03456856
A Study of Ivabradine in African-American/ Black Subjects With Heart Failure and Left Ventricular Systolic Dysfunction.
A Phase 4 study testing Ivabradine in people with Heart Failure (HF), run by Amgen at 3 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Heart Failure (HF)
- What is being tested?
- Ivabradine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 3 sitesUnited States
- Study dates
- 28 Sep 2017to 20 May 2019
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 27Show fewer
- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Research Site
Buffalo, New York, 14215
Research Site
Detroit, Michigan, 48202
Research Site
Wilmington, Delaware, 19803
About this study
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
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.
Read the 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)
- Being tested
- Ivabradine
- Keywords
- Cardiac, Congestive, Decompensation, Heart Failure, Left-Sided, Myocardial, Corlanor, Ivabradine, African American, Black, Michigan
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IvabradineDrug
Also called Corlanor®
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.
| Study group | Role | What they receive |
|---|---|---|
| Ivabradine | Experimental | 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. Receives: Drug: Ivabradine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Heart Rate (HR) at Day 57
Summary is based on observed data, and no imputation is used for missing values.
Least-square mean is from the repeated measures model which includes scheduled visits and baseline HR measurement as covariates.
The mean change from baseline in heart rate is compared to -5 beats/min which is observed in the placebo group in the Systolic Heart Failure Treatment with the IF Inhibitor Ivabradine Trial (SHIFT) study ( NCT02441218, PMID 20801500).
Measured: Day1 (baseline), Day 57
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2018
- Study start28 Sep 2017
- Primary completion19 Apr 2019
- Study completion20 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart Failure (HF)Studies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03456856
- Sponsor's protocol ID
- 20160231
- Status last verified
- Oct 2021
- First submitted
- 1 Mar 2018
- Last updated
- 28 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Publications
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.
PubMed 32808163
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03456856
- Acronym / sponsor ID
- 20160231
- Conditions
- Heart Failure (HF)
- Keywords
- Cardiac, Congestive, Decompensation, Heart Failure, Left-Sided, Myocardial, Corlanor, Ivabradine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 28 Sep 2017 (actual)
- Primary completion
- 19 Apr 2019 (actual)
- Study completion
- 20 May 2019 (actual)
- First posted
- 7 Mar 2018 (actual)
- Results
- Posted 7 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ivabradine | Experimental | Drug: IvabradineThe 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. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (27 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IvabradineAlso: Corlanor®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. | Drug | Ivabradine |
Primary outcome
Change From Baseline in Heart Rate (HR) at Day 57
Time frame: Day1 (baseline), Day 57
Summary is based on observed data, and no imputation is used for missing values. Least-square mean is from the repeated measures model which includes scheduled visits and baseline HR measurement as covariates. The mean change from baseline in heart rate is compared to -5 beats/min which is observed in the placebo group in the Systolic Heart Failure Treatment with the IF Inhibitor Ivabradine Trial (SHIFT) study ( NCT02441218, PMID 20801500).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 32808163Lanfear 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.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ivabradine in people with Heart Failure (HF), run by Amgen at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Heart Rate (HR) at Day 57 (time frame: Day1 (baseline), Day 57). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03456856, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2021.