Efforts to contain rising costs for hospital acute care have resulted in shorter hospital
stays for patients with acutely decompensated heart failure. These shorter stays may not
allow for adequate diuresis, titration of oral medications, or for patients to receive the
full benefit of intravenously (IV) administered medications. In addition to shorter stays
when hospitalized, physicians are exploring ways to treat patients in the outpatient setting
to avoid hospitalization. Although there is increasing interest among clinicians in the use
of outpatient IV therapy for the treatment of advanced heart failure, there is no consensus
among clinicians regarding patient selection, dosing, or treatment duration. The use of IV
inotropic agents (drugs that influence and or affect muscle contractility) such as milrinone
or dobutamine in this setting is controversial and may lead to increased mortality. Indeed,
the ACC/AHA (American College of Cardiology and American Hospital Association) guidelines
warn that long-term intermittent use of IV inotropes for treatment of left ventricular
dysfunction is of "unproved value and not recommended." Yet, despite these guidelines,
clinicians use inotropes in the outpatient setting because there is no currently approved
alternative therapy. Thus, there is an unmet need for effective outpatient treatment of
advanced chronic heart failure to improve quality of life and/or reduce the number of
hospital admissions for heart failure.
The data from previous studies suggest that doses of NATRECOR® hBNP may be a potent agent for
the treatment of acute congestive heart failure (CHF) with a unique combination of desirable
effects on the flow of blood throughout the body; the hormones secreted by the nervous system
and support of copious salt outputs by the renal system not provided by currently available
therapies. This study is a multicenter, open-label pilot study in which subjects who have
received treatment for acutely decompensated CHF during a hospitalization at least twice
within the previous 12 months are randomized (1:1:1) to one of three treatment groups. One
treatment group will receive their usual long term cardiac medications, either with or
without serial infusions of inotropes (various drugs that affect the strength of contractions
of the heart muscle) and without nesiritide therapy. The 0.005 mcg/kg/min nesiritide
treatment group receives a 0.5 mcg/kg bolus of nesiritide followed by a 0.0025 mcg/kg/min
infusion, in addition to their usual long term cardiac medications, excluding IV inotropes;
The 0.010 mcg/kg/min nesiritide treatment group receives a 1 mcg/kg bolus of nesiritide
followed by a 0.005 mcg/kg infusion, in addition to their usual long term cardiac
medications, excluding IV inotropes. Because patients treated in an outpatient setting may be
less decompensated than patients with acutely decompensated heart failure, this study was
designed to evaluate the 0.010 mcg/kg/min dose of nesiritide (the currently approved dose for
acutely decompensated patients) as well as a lower dose (0.005 mcg/kg/min).
The hypothesis is that as an adjunct therapy to oral medications, serial IV infusions of
nesiritide may produce more rapid and sustained compensation of heart failure in patients
with frequent episodes of decompensated heart failure. The 0.005 mcg/kg/min group receives a
0.5 mcg/kg bolus followed by a 0.0025 mcg/kg/min infusion; the 0.010 mcg/kg/min group
receives a 1 mcg/kg bolus followed by a 0.005 mcg/kg infusion. Intravenous bolus over 60
seconds and a fixed rate infusion of 4 - 6 hours, at least once per week for 12 weeks.