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

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

Interventions

DRUG

Ivabradine

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.

DRUG

Placebo

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.

Sponsors & Collaborators

• Amgen

  collaborator INDUSTRY

• iRhythm Technologies, Inc.

  collaborator INDUSTRY

• Phillip Levy

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

19 Years

Max Age

89 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-07-01

Primary Completion

2020-07-31

Completion

2021-12-31

FDA Drug

Yes

Countries

• United States

Study Locations