Trial Assessing the Effectiveness of Ivabradine Started at Discharge From the Observation Unit

NCT03168529 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: 1701000235
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

Ivabradine (IVA) has been shown to decrease the risk of hospitalizations for worsening Heart Failure and was associated with a trend towards improved mortality in the SHIFT1 trial. SHIFT1 excluded patients within 4 weeks of hospital discharge, so the efficacy and safety of IVA in this setting is less clear. In today's health care environment more and more patients that present to the Emergency Department (ED) for mild Acute Heart Failure (AHF) are being placed into observation unit and subsequently discharged, or discharged outright from the ED. This is not only a growing segment of patients, but also represents an important window of opportunity to intervene with a potentially effective therapy. Moreover, at this point in a patient's experience (being discharged after getting treated for exacerbation of Heart Failure), it's not clear that beta blockers (BB) should yet be increased/started due to the recent state of exacerbation. Standard treatment of worsened heart failure presenting to the ED or urgent care includes diuretics (e. g. furosemide) and vasodilators (e.g. ACE-I, ARB, Hydralazine/Isosorbide or ARNi), but according to usual standard of care, titration of beta blockade is often reserved for outpatient follow up after a period of demonstrated stability (in the ambulatory setting). This is in contradistinction to hospitalized patients, where patients have been observed by the treating team for days, presumably show stability and improvement, and starting low dose BB at the time of hospital discharge has been shown to be safe. As such these ED/Observation discharge patients are often not optimal candidates for intensification of BB at the time of release, and could be considered to be at maximally tolerated BB dose (for at least for 2-4 weeks). This may represent a vulnerable period for these patients; its unknown in the setting of Observation discharge but evidence from hospitalized patients indicates that the highest daily risk of rehospitalization is in the days just after discharge. IVA may be effective post observation unit management (where lower risk Heart Failure (HF) patients are typically placed), to reduce heart rate (without decreasing contractility, such as a BB would) to help reduce the risk of hospitalization or emergency care, but safety and efficacy (in terms of heart rate lowering) in this setting has not been previously explored. Additionally, the SHIFT1 trial lacked African Americans and this unique patient population has not been previously studied with IVA. The investigating sites serve a predominantly African American patient population. Therefore the proposed study represents an important opportunity to gather data on IVA effect in this understudied group of patients.

Conditions

Heart Failure

Keywords

Acute Heart Failure; Observation; Ivabradine

Outcome Measures

Primary Outcomes (1)

• Change in Heart Rate

  Change in heart rate from final visit to baseline visit, measured by 12-lead ECG and Zio® patch.

  Heart rate to be recorded at baseline, day 14 (+/-1), and day 28 (+/-2).

Secondary Outcomes (1)

• Change in Heart Rate in Self-identified African Americans

  Heart rate to be recorded at baseline, day 14 (+/-1), and day 28 (+/-2).

Other Outcomes (3)

• Change in NT-proBNP

  Biomarkers will be drawn at baseline and at day 28 (+/-2).

• Change in Hs-TnT

  Biomarkers will be drawn at baseline and at day 28 (+/-2).

• Safety: Unplanned Medical Care

  Recording of unplanned medical visits from baseline to final visit (Day 28 (+/- 2)).

Study Arms (2)

Ivabradine (Corlanor)

ACTIVE COMPARATOR

All subjects will complete the same number of follow-ups, dose titrations (if necessary) and study procedures however, subjects in this arm will be receiving active drug for study duration.

Drug: Ivabradine

Placebo

PLACEBO COMPARATOR

All subjects will complete the same number of follow-ups, dose titrations (if necessary) and study procedures however, subjects in this arm will be receiving placebo for study duration.

Drug: Placebo

Interventions

Ivabradine DRUG

At discharge from the observation unit, subjects will receive a pill bottle containing oral capsules containing active drug to take at home. This arm will require the subject to take the study medication BID for the duration of the study period. Neither study team nor subject will know if the pill bottle contains active drug or placebo.

Also known as: Corlanor

Ivabradine (Corlanor)

Placebo DRUG

At discharge from the observation unit, subjects will receive a pill bottle containing oral capsules not containing active drug to take at home. This arm will require the subject to take the study medication BID for the duration of the study period. Neither study team nor subject will know if the pill bottle contains active drug or placebo.

Placebo

Eligibility Criteria

• Age: 19 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 and \<90.
• Established HF with reduced ejection fraction (EF ≤35 %), assessment done within 12 months of index visit.
• Admitted under observation unit for management of AHF.
• Heart rate ≥70 beats per minute, with sinus rhythm.
• Receiving guideline based medical therapy in the judgement of the treating physician.
• Patient currently on a Beta Blocker regimen. Achieved clinically determined stabilization during treatment under observation unit such that the treating physician is planning to discharge home without hospital admission.

You may not qualify if:

• Known intolerance to study drug.
• End stage renal disease.
• Plan to titrate BB at the time of discharge from the observation unit.
• Any condition that in the opinion of the investigators will interfere with the ability to complete the study (e.g. history of extreme non-adherence, extreme psychosocial instability).
• Inability to provide written informed consent.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (women of childbearing age will be included only if they agree to use adequate contraceptive methods or engage in sexual abstinence).
• Systolic Blood pressure less than 100 mmHg.
• Sick sinus syndrome, sinoatrial block or 3rd degree AV block, unless a functioning demand pacemaker is present.
• Severe hepatic impairment.
• Pacemaker dependence (i.e. heart rate maintained exclusively by the pacemaker).
• Concomitant use of strong CYP3A4 inhibitors. Examples of strong CYP3A4 inhibitors include azole antifungals (e.g., itraconazole), macrolide antibiotics (e.g., clarithromycin, telithromycin), HIV protease inhibitors (e.g., nelfinavir), and nefazodone.
• Concomitant use of diltiazem or verapamil that are not planned for discontinuation.
• Severe, left sided valvular abnormalities (severe aortic stenosis, severe mitral stenosis, severe aortic insufficiency or severe mitral regurgitation.
• Documented, prior to or at the time of randomization, restrictive amyloid cardiomyopathy, or acute myocarditis, or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy.

Sponsors & Collaborators

• Phillip Levy: lead
• Amgen: collaborator
• iRhythm Technologies, Inc.: collaborator

Study Sites (2)

Wayne State University

Detroit, Michigan, 48201, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Related Publications (2)

• Bohm M, Robertson M, Borer J, Ford I, Komajda M, Mahfoud F, Ewen S, Swedberg K, Tavazzi L. Effect of Visit-to-Visit Variation of Heart Rate and Systolic Blood Pressure on Outcomes in Chronic Systolic Heart Failure: Results From the Systolic Heart Failure Treatment With the If Inhibitor Ivabradine Trial (SHIFT) Trial. J Am Heart Assoc. 2016 Feb 12;5(2):e002160. doi: 10.1161/JAHA.115.002160.

  PMID: 26873681 BACKGROUND

• Gattis WA, O'Connor CM, Gallup DS, Hasselblad V, Gheorghiade M; IMPACT-HF Investigators and Coordinators. Predischarge initiation of carvedilol in patients hospitalized for decompensated heart failure: results of the Initiation Management Predischarge: Process for Assessment of Carvedilol Therapy in Heart Failure (IMPACT-HF) trial. J Am Coll Cardiol. 2004 May 5;43(9):1534-41. doi: 10.1016/j.jacc.2003.12.040.

  PMID: 15120808 BACKGROUND

MeSH Terms

Conditions

Heart Failure

Interventions

Ivabradine

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Phillip Levy, MD
• Organization: Wayne State University

plevy@med.wayne.edu

3135771214

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Subjects will be randomized at baseline, then at discharge dispensed a uniquely coded IP bottle. The randomization numbers to each IP bottle will be generated and maintained in an outside dataset or randomization key. The subject ID and corresponding randomization number, recorded in REDCap, will correlate which subjects are in each group, Ivabradine or placebo. In the case of an emergent medical event, where the unblinding of a subject is deemed medically necessary by the study PIs, the unblinded study personnel will consult the randomization key to unblind study treatment. Once a subject has been unblinded, the date, time and reason(s) for un-blinding will be recorded in the source documents and eCRF.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Edward S. Thomas Endowed Professor and Associate Chair of Research, Department of Emergency medicine

Model Details: Prospective, randomized (1:1), placebo-controlled, double blind, study of ivabradine (Corlanor®)

Study Record Dates

• First Submitted: May 24, 2017
• First Posted: May 30, 2017
• Study Start: July 1, 2018
• Primary Completion: July 31, 2020
• Study Completion: December 31, 2021
• Last Updated: June 8, 2025
• Results First Posted: June 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)