STOCKHOLM — A natriuretic peptide was safe and effective for treating patients with acute, decompensated heart failure in a phase II study with a total of 221 patients.
Ularitide, given intravenously, reduced pulmonary capillary wedge pressure, improved dyspnea, and did not worsen renal function when given to patients for 24 hours of continuous infusion, Veselin Mitrovic, M.D., said at the annual congress of the European Society of Cardiology.
A synthetic form of a natriuretic peptide made in human kidneys, ularitide, “was associated with a seemingly greater hemodynamic effect than nesiritide [Natrecor], but this must be validated by a direct comparison,” commented Marco Metra, M.D., a professor of cardiology at the University of Brescia (Italy).
The study enrolled patients with symptomatic decompensated heart failure and a pulmonary capillary wedge pressure (PCWP) of at least 18 mm Hg. They were randomized to treatment with one of three dosages of ularitide or placebo. The drug dosages were 7.5, 15, or 30 ng/kg per minute. The study was done at 19 centers in Germany, Russia, and Serbia.
One primary end point was the change from baseline in PCWP after 6 hours of treatment. All three ularitide dosages resulted in significantly larger declines in PCWP, compared with patients treated with placebo. In the two groups that received the largest ularitide dosages, the average drop in PCWP was about 10 mm Hg, reported Dr. Mitrovic, medical director of the research unit at the Kerckhoff Clinic in Bad Nauheim, Germany.
The second primary end point was patients' self-assessed improvement in dyspnea after 6 hours of treatment. About 45% of the patients who received either of the two highest dosages reported a moderate or marked improvement in their dyspnea, compared with 38% who reported this degree of improvement on the lowest dosage, and 25% with this level of improvement in the placebo group.
Ularitide also produced a dose-related increase in cardiac index and a reduction in systemic vascular resistance.
The drug had no detectable impact on urine output, serum creatinine level, or creatinine clearance. The apparent absence of an effect on kidney function may mean that ularitide acts differently from nesiritide. Evidence from a metaanalysis published earlier this year indicated that a single dose of nesiritide worsens renal function in some patients with acute, decompensated heart failure (Circulation 2005;111:1487–91).
In the new study, treatment with ularitide was associated with fewer serious adverse events and fewer deaths, compared with the placebo group.
The short- and long-term effects of ularitide must be further examined in larger studies that allow assessment of morbidity and mortality events as the primary end points, Dr. Metra said.
The new results did not establish the optimal ularitide dosage, Dr. Mitrovic said. The 30 ng/kg per minute dosage may be best suited for patients with a relatively high systemic blood pressure at baseline, he said. A lower dosage, such as 15 ng/kg per minute, might work best for patients with a lower systemic blood pressure at the start of treatment.
The study was sponsored by Protein Design Labs, which holds worldwide development and marketing rights for ularitide.