Effects of the renal natriuretic peptide urodilatin (ularitide) in patients with decompensated chronic heart failure: a double-blind, placebo-controlled, ascending-dose trial.

BACKGROUND

Urodilatin (ularitide), a natriuretic peptide, is produced within the kidneys. The aim of this study was to define the role of 24-hour intravenous infusions of urodilatin in the treatment of decompensated chronic heart failure (DHF).

METHODS

In this randomized, double-blind, ascending-dose safety study, 24 patients with DHF (cardiac index 1.91 +/- 0.34 L/min per square meter, pulmonary capillary wedge pressure 26 +/- 6 mm Hg, right atrial pressure 11 +/- 4 mm Hg) received urodilatin (7.5, 15, or 30 ng/(kg.min)) or placebo infusions over 24 hours.

RESULTS

Compared with baseline, urodilatin decreased pulmonary capillary wedge pressure by 10 mm Hg in the 15 ng/(kg.min) group (P < .05) and by 15 mm Hg in the 30 ng/(kg.min) group (P < .05) at 6 hours. In the same dose groups, right atrial pressure decreased, and dyspnea as reported by patients tended to improve. At 24 hours, 15 and 30 ng/(kg.min) urodilatin infusions decreased N-terminal-pro-brain natriuretic peptide levels by 40% and 45%, respectively, compared with baseline. Between 1 to 12 hours, plasma cyclic guanosine monophosphate levels at 15 and 30 ng/(kg.min) urodilatin were significantly higher than both placebo and the respective baseline after infusion start (P < .05 and .01). Among the different groups, there was no obvious difference regarding total number of patients with adverse events and total number of adverse events. During infusion, 3 transient asymptomatic hypotensions occurred in the urodilatin groups.

CONCLUSIONS

Our findings show that urodilatin may be a new agent for the therapy for DHF.