Healthcare Industry News: Mitral Valve
News Release - May 9, 2006
Investigators Report Findings of a Phase 2 Pilot Study Evaluating Postoperative Renal Effects in Heart Failure Patients Treated with NesiritideFREMONT, Calif., May 9 (HSMN NewsFeed) -- Investigators reported results of a Scios Inc. sponsored pilot trial that included information about the safety of the heart failure drug nesiritide on postoperative renal function and clinical outcomes in heart failure patients who required coronary artery bypass graft (CABG) surgery using cardiopulmonary bypass. The study findings were presented at the 7th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke meeting in Washington, D.C. Nesiritide is indicated for the intravenous treatment of patients with acutely decompensated congestive heart failure who have dyspnea at rest or with minimal activity.
The NAPA (Nesiritide Administered Peri-Anesthesia in Patients Undergoing Cardiac Surgery) trial was a prospective, multi-center, randomized, double- blind, pilot study that included 279 randomized and treated heart failure patients from 54 centers undergoing cardiac surgery with or without Mitral Valve repair/replacement. In this study, patients with reduced heart pumping function who were scheduled for CABG surgery utilizing cardiopulmonary bypass were randomized to be treated with an infusion of nesiritide or placebo after induction of anesthesia in addition to usual care for 24 to 96 hours. Renal function was measured through hospital discharge or study day 14 (whichever came first). As a Phase 2 study there were no prespecified endpoints; however exploratory analyses were conducted for primary and secondary areas of interest. Patients undergoing CABG plus an aortic valve procedure were excluded from the study.
The maximum mean increase in serum creatinine (SCr) from baseline (during hospitalization or by study day 14, was 0.15+/-0.29 mg/dL in nesiritide patients compared to 0.34+/-0.48 mg/dL in placebo patients (P<0.001). This difference was even greater in patients who had some degree of renal dysfunction before surgery. The maximum decrease in glomerular filtration rate (GFR) from baseline was -10.8 mL/min/1.73 m2 in nesiritide patients compared to -17.2 mL/min/1.73 m2 in placebo patients (P=0.001).
"Renal function is a significant concern of doctors for patients undergoing heart surgery," said Dr. Hebeler, NAPA investigator from Baylor University Medical Center. "Depending on the patient population and the definitions used, as many as 25 or 30% of patients undergoing cardiac surgery have deterioration of renal function postoperatively. These trial results are important and warrant further evaluation because in this study the use of nesiritide favorably affected renal function following surgery."
Although the use of intravenous diuretic medications was similar between the two groups, urine output 24 hours after admission to an Intensive Care Unit was greater in patients receiving nesiritide than placebo (2926 mL in nesiritide patients compared to 2350 mL in placebo patients, P<0.001). Nesiritide patients also had a shorter hospital length of stay compared to the placebo group (9.1+/-6.1 days compared to 11.4+/-9.8 days, P=0.043).
"These important data provide additional information about the safety profile of nesiritide in this patient population. Scios is committed to helping heart failure patients and to continuing to conduct clinical trials with nesiritide to explore potential patient benefits," said Roger M. Mills, MD, Vice President, Medical Affairs, Scios Inc.
These results will be included in the May 30, 2006 online issue of Circulation. The NAPA investigators plan to present additional data from the study in the fall of this year.
Prospectively identified primary areas of interest that did not show statistically significant differences in this study were: use of intravenous vasoactive medications and significant changes in hemodynamics. Prospectively identified secondary areas of interest that did not show statistically significant differences in this study were: Intensive Care Unit length of stay and duration of intubation.
About NATRECOR® (nesiritide)
NATRECOR® is indicated for the intravenous treatment of patients with acutely decompensated congestive heart failure who have dyspnea at rest or with minimal activity. In this population, the use of NATRECOR® reduced pulmonary capillary wedge pressure and improved dyspnea. For full Prescribing Information, visit www.natrecor.com.
About Scios Inc.
Scios Inc., a Johnson & Johnson company, is a biopharmaceutical company headquartered in Fremont, California. Scios 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 www.sciosinc.com.
IMPORTANT SAFETY INFORMATION
NATRECOR® (nesiritide) may cause hypotension and should be administered only in settings where blood pressure can be monitored closely. If hypotension occurs during administration of NATRECOR® the dose should be reduced or discontinued. At the recommended dose of NATRECOR®, the incidence of symptomatic hypotension (4%) was similar to that of IV nitroglycerin (5%). Asymptomatic hypotension occurred in 8% of patients treated with either drug. In some cases, hypotension that occurs with NATRECOR® may be prolonged. The mean duration of symptomatic hypotension was longer with NATRECOR® than IV nitroglycerin (2.2 versus 0.7 hours, respectively). NATRECOR® should not be used in patients with systolic blood pressure <90 mm Hg or as primary therapy in patients with cardiogenic shock. The rate of symptomatic hypotension may be increased with a baseline blood pressure <100 mm Hg, and NATRECOR® should be used cautiously in these patients. In earlier trials, when NATRECOR® was initiated at doses higher than the 2 mcg/kg bolus followed by a 0.01 mcg/kg/min infusion, the frequency, duration, and intensity of hypotension was increased. The hypotensive episodes were also more often symptomatic and/or more likely to require medical intervention. NATRECOR® is not recommended for patients for whom vasodilating agents are not appropriate and should be avoided in patients with low cardiac filling pressures.
NATRECOR® may affect renal function in susceptible individuals. In patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with NATRECOR® may be associated with azotemia. In the VMAC trial, through day 30, the incidence of elevations in creatinine to >0.5 mg/dL above baseline was 28% and 21% in the NATRECOR® and nitroglycerin groups, respectively. When NATRECOR® was initiated at doses higher than 0.01 mcg/kg/min, there was an increased rate of elevated serum creatinine over baseline compared with standard therapies, although the rate of acute renal failure and need for dialysis was not increased.
In seven NATRECOR® clinical trials, through 30 days, 5.3% in the NATRECOR® treatment group died as compared with 4.3% in the group treated with other standard medications. In four clinical trials, through 180 days, 21.7% in the NATRECOR® treatment group died as compared with 21.5% in the group treated with other medications. There is not enough information to know if there is an increased risk of death after treatment with NATRECOR®.
See full Prescribing Information at www.natrecor.com.
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