The SIRIUS II trial of the synthetic natriuretic peptide ularitide as treatment for patients with acute decompensated heart failure indicates that the drug may be an effective new therapy for these patients, according to a presentation at the annual meeting of the European Society of Cardiology. The natural peptide, which is produced in the kidney, is called urodilatin.

"The results of the SIRIUS II study show ularitide to be well-tolerated and indicate clear, dose-dependent favorable effects in treating the symptoms of acute decompensated heart failure without compromising kidney function," said Veselin Mitrovic, MD, Medical Director of the Research Unit / Kerckhoff Clinic, Bad Nauheim. "Based on the overall findings, ularitide holds potential as a treatment for [ADHF] patients."

The SIRIUS II trial was a randomized, double-blind, placebo-controlled clinical trial conducted at 19 European centers. A total of 221 patients were randomized to ularitide 7.5, 15, or 30 ng/kg/min given intravenously as a 24-hour infusion or to placebo.

The two primary endpoints were change in dyspnea score and change in pulmonary capillary wedge pressure at six hours. Secondary endpoints included serum creatinine levels, length of hospital stay, and mortality.

Ularitide treatment was associated with a significantly improved dyspnea score (p<0.05) in all three dosing groups compared with placebo. Dyspnea was assessed using a standard dyspnea scale, which measures a patient's perception of their change in shortness of breath from the start of drug therapy. More patients reported moderate to marked improvement in dyspnea in all of the three treatment groups compared with placebo.

The findings also demonstrated a significant decrease in pulmonary pressure (p<0.05) as measured by pulmonary capillary wedge pressure at six hours. These changes were also associated with an increase in cardiac index in the 15 and 30 ng/kg/min groups. At six hours, wedge pressure dropped 10-12 mmHg on average from baseline for those treated with ularitide, compared with those on placebo, for whom PCWP dropped 4 mmHg from baseline.

Serum creatinine levels were unchanged in patients treated with ularitide compared with placebo through 72 hours. This finding suggests that ularitide did not negatively affect kidney function in study patients. Length of hospital stay, measured in median hours in hospital, was lower for the 15 and 30 ng/kg/min groups compared with the placebo and 7.5 ng/kg/min groups. The length of hospital stay was lowest for the 15 ng/kg/min (122 hours) and 30 ng/kg/min (158 hours) groups, compared with placebo (200.5 hours) and 7.5 ng/kg/min (192 hours) groups.

The mortality rate through day 30 was higher in the placebo group than in the three ularitide groups: 13.2 percent in the placebo group and 3.3 percent (p=0.080, compared to placebo), 3.8 percent (p=0.16), and 1.8 percent (p=0.029) in the 7.5, 15 and 30 ng/kg/min groups, respectively.