Interleukin-1 Receptor Antagonist for the Treatment of Heart Failure in Patients With Left Ventricular Assist Devices

More than 5 million Americans have heart failure, a number that is expected to increase 25%
by the year 2030. Fifty percent of individuals diagnosed with heart failure die within 5
years of diagnosis. Of those patients who currently have heart failure, 5-10% have Stage D
disease, requiring specialized interventions such as chronic inotropic support, mechanical
circulatory support, or transplantation. Transplantation is considered curative for heart
failure, but only about 2,200 heart transplants take place each year. Due to the imbalance
between donors and possible recipients, a large number of patients remain who could benefit
from transplantation that will never receive a heart. Many patients receive left ventricular
assist devices (LVADs) to support their failing hearts, increasing their chances of survival
while they wait to undergo transplantation.

It has been shown that up to 19% of patients show durable echocardiographic recovery (as
measured by left ventricular ejection fraction >40%) after ventricular unloading with an
LVAD. Recovery mediated by unloading with the LVAD causes several changes at the molecular
level. However, the mechanisms underlying recovery at the cellular level, also known as
reverse remodeling, are only recently being studied. Thus, the window of opportunity to
develop adjuvant treatments to enhance recovery is just now opening.

Interestingly, patients that experience durable echocardiographic recovery have higher
circulating levels of anti-inflammatory cytokines. Inhibition of inflammatory cytokines,
such as with the use of receptor antagonists for inflammation-associated cytokines like
Anakinra, has also been shown to reduce adverse myocardial remodeling after ischemic events
and to increase exercise activity in patients with systolic heart failure. This study
proposes the exogenous administration of Anakinra to end-stage heart failure patients
supported with LVADs in an effort to increase both the number of patients who experience
recovery and the magnitude of recovery.

While this is a small trial aimed primarily at demonstrating biologic efficacy of Anakinra,
clinical efficacy in this study is also investigated. Encouraging results in this pilot
study may prompt the creation of a randomized, controlled trial designed to demonstrate
efficacy from a functional clinical standpoint.

Inclusion Criteria:

- To qualify for inclusion, patients must meet the following criteria: age >18 years at
date of LVAD implantation who require circulatory support with an LVAD for either a
bridge-to-transplant or destination therapy indication.

- They must also be judged by the implanting surgeon to have an expected survival to
trial completion (approximately 6 months after implantation), without regard to the
likelihood of cardiac transplantation.

Exclusion Criteria:

- Exclusion criteria include the presence of a Right Ventricular Assist Device, as
biventricular support is associated with decreased survival outcomes that could
negatively impact the attrition rate over the course of the study.

- Additional exclusion criteria include the inability of the patient or a trained
caregiver to administer the study drug, and inability of the patient to complete the
study questionnaire. - Patients with a creatinine clearance < 30 mL/min, evidence of
an active infection, immunosuppression, or with an allergy to E. Coli derived
products will also be excluded. -

- Last, any patient with dependence on inflammatory modulating drugs will be excluded.