Elsevier

American Heart Journal

Volume 150, Issue 6, December 2005, Pages 1239.e1-1239.e8
American Heart Journal

Clinical Investigation
Congestive Heart Failure
Effects of the renal natriuretic peptide urodilatin (ularitide) in patients with decompensated chronic heart failure: A double-blind, placebo-controlled, ascending-dose trial

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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.

Section snippets

Study design

This double-blind, placebo-controlled, ascending-dose study in patients with DHF was performed in 2 centers. For safety reasons, patients were randomly assigned to 3 urodilatin-dose groups (7.5, 15, and 30 ng/(kg · min)) in ascending order, beginning with 7.5 ng/(kg · min). In each dose group, 6 patients were treated with urodilatin and 2 patients with placebo.

All patients received their basal cardiovascular medication. During a 5-hour period (beginning 3 hours before start of study drug

Concomitant cardiac medication

Twenty-four patients were enrolled in 2 centers. Patients' basal cardiovascular medications included oral loop diuretics, thiazides, ACE inhibitors/angiotensin I blockers, β-blockers, spironolactone, and glycosides. Patients of the placebo and the 7.5 ng/(kg · min) groups more frequently received as basal medication hemodynamically acting nitrates and loop diuretics (Table I, Table III). IV dopamine infusions were ongoing at constant rates in 1 patient of the placebo and 1 in the 7.5 ng/(kg ·

Discussion

In this study, 24-hour infusions of ascending urodilatin doses result in beneficial hemodynamic and neurohumoral effects in patients with DHF. This is the first report on the treatment of DHF using a 24-hour urodilatin infusion.

Urodilatin in a dose of 30 ng/(kg · min) causes substantial decreases in PCWP and RAP compared with placebo at 6 hours, whereas in the 7.5 ng/(kg · min) group, no effect of urodilatin is observed. Urodilatin exerts vasodilatory effects.6 Therefore, decreased cardiac

References (21)

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Hartmut Lüss, Erik Maronde, Katrin Fricke, Kristin Forssmann, Wolf-Georg Forssmann, and Markus Meyer are CardioPep Pharma employees. Veselin Mitrovic and Klaus Nitsche received consultant fees from CardioPep Pharma.

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