Study of Safety and Tolerability of Outpatient IV Infusions of NATRECOR(reg) (nesiritide)

Main Category: Cardiovascular / Cardiology
Article Date: 02 Sep 2004 - 10:00 PDT


Scios Inc announced the publication of results from a multi-center clinical study of the safety and tolerability of intravenous (IV) infusions of NATRECOR(reg) (nesiritide) in advanced decompensated congestive heart failure patients in an outpatient setting. The results of the FUSION I (Follow Up Serial Infusions Of NATRECOR(reg)) study, a controlled study of outpatient IV infusion therapy conducted in heart failure patients, were published today in the September 1, 2004 issue of The American Journal of Cardiology.

According to the American Heart Association Heart Disease and Stroke Statistics - 2004 Update, congestive heart failure affects more than five million Americans. It is estimated that the cost of treating congestive heart failure patients in the U.S. will reach $28.8 billion in 2004.

Study Details and Results

FUSION I was a multi-center (46 U.S. sites), randomized, open-label, pilot safety study of 210 advanced decompensated congestive heart failure patients at high risk for rehospitalization. Patients were randomized to receive either standard care (usual long-term cardiac medications with or without IV inotropes) or infusions of NATRECOR(reg) at dosages of 0.005 or 0.01 mcg/kg/min (in addition to their usual long-term cardiac medications, excluding IV inotropes) for 12 weeks. Based on patient symptoms, the infusion frequency could vary from once every other week to twice a week.

Patients were further classified as low risk or high risk based on seven clinical criteria (patients with four or more of these criteria were considered high risk). All patients had weekly outpatient visits for 12 weeks. NATRECOR(reg) infusions took place over four to six hours. Patients were observed for an additional period of four weeks after completion of the three-month treatment period.

The incidence of adverse events through 12 weeks was similar in the three groups, and no adverse event occurred significantly more frequently in the patients treated with NATRECOR(reg). Less than one percent (11 of 1,645 infusions) of NATRECOR(reg) infusions were discontinued during a study visit due to side effects.

Through week 12, 48 percent of NATRECOR(reg) and 58 percent of standard care patients either died or were hospitalized (p=0.185). Through the same period, six percent of NATRECOR(reg) and 10 percent of standard care patients died (p=0.314); 46 percent of NATRECOR(reg) and 54 percent of standard care patients were hospitalized (p=0.378). Within the higher risk stratum, patients treated with NATRECOR(reg) had a statistically significant reduction in death and hospitalization (52 versus 78 percent; p=0.038) and in the number of days that patients were alive and out of the hospital (77 versus 67 days; p=0.027) compared to standard care. Within the higher risk stratum, five percent of NATRECOR(reg) patients and 17 percent of standard care patients died (p=0.079) through week 12.

"Caring for heart failure patients places an enormous burden on our nation's hospitals, and a disproportionate share of that burden is caused by those patients with advanced disease. FUSION is investigating precisely this patient population," said Clyde W. Yancy, M.D., professor of Medicine & Cardiology, director of Congestive Heart Failure/Heart Transplant Program at the University of Texas Southwestern Medical Center, Dallas, and principal investigator of the FUSION study. "Based on these peer-reviewed results and initial observations, we are now conducting the FUSION II study to further explore whether once or twice weekly infusions of nesiritide in the outpatient setting have the potential to reduce mortality and rehospitalization."

About Decompensated Congestive Heart Failure

Congestive heart failure is characterized by a progressive loss in the heart's ability to pump blood. Since a weak heart does not pump fluid very well through the body, fluid can back up and "pool" in the lungs causing shortness of breath or can accumulate in the ankles causing swelling. This is why heart failure is often called "congestive" heart failure, or CHF. The term "decompensated" is a medical term used to describe patients with these symptoms.

About NATRECOR(reg)

NATRECOR(reg) (nesiritide) is indicated for the treatment of acutely decompensated congestive heart failure in patients with dyspnea (shortness of breath) at rest or with minimal activity. Administered intravenously, NATRECOR(reg) is a recombinant form of human B-type natriuretic peptide (hBNP), a naturally occurring peptide produced by the heart. In clinical trials, NATRECOR(reg) caused arteries and veins to dilate, alleviating symptoms in patients with acutely decompensated congestive heart failure by improving circulation, without increasing heart rate or interfering with heartbeat regularity.

NATRECOR(reg) may cause hypotension. If hypotension occurs during administration of NATRECOR(reg), the dose should be reduced or discontinued and blood pressure should be monitored closely. At the recommended dose of NATRECOR(reg), the incidence of symptomatic hypotension (four percent) was similar to that of IV nitroglycerin (five percent). Asymptomatic hypotension occurred in eight percent of patients treated with either drug. The mean duration of symptomatic hypotension was longer with NATRECOR(reg) than IV nitroglycerin (2.2 versus 0.7 hours, respectively). NATRECOR(reg) may affect renal function in susceptible patients. In patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with NATRECOR(reg) may be associated with azotemia.

Other adverse events reported at a rate of at least five percent during the first 24 hours of infusion with either NATRECOR(reg) plus standard care or IV nitroglycerin plus standard care therapy, included, respectively: ventricular tachycardia (three percent, five percent), nonsustained ventricular tachycardia (three percent, five percent), headache (eight percent, 20 percent), abdominal pain (one percent, five percent), and nausea (four percent, six percent). Higher doses of NATRECOR(reg) increased the risk of hypotension and elevated creatinine. NATRECOR(reg) should be avoided as primary therapy in patients with cardiogenic shock, systolic blood pressure 90 mm Hg, or in patients with low cardiac filling pressures. Please refer to www.natrecor.com for full prescribing information.

About Scios Inc.

Scios Inc., a member of the Johnson & Johnson Family of Companies, is a biopharmaceutical company headquartered in Fremont, California. Scios Inc. is developing novel treatments for cardiovascular disease, inflammatory disease and cancer. The company's disease-based technology platform integrates expertise in protein biology with computational and medicinal chemistry to identify novel targets and rationally design small molecule compounds and peptides for markets with unmet medical needs. For more information, visit http://www.sciosinc.com.

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