Assessment of the Efficacy and Safety of Intravenous Conivaptan in Euvolemic and Hypervolemic Hyponatremia

American Journal of Nephrology - Tập 27 Số 5 - Trang 447-457 - 2007
David Zeltser1, Steven J. Rosansky2, Hannes van Rensburg3, Joseph G. Verbalis4, Neila Smith5
1Department of Internal Medicine D, Sourasky Medical Center, Tel Aviv, Israel
2Department of Internal Medicine, WJB Dorn Veterans Hospital, Columbia, S.C.,
3Unitas Hospital, Lyttelton Manor, South Africa
4Department of Medicine, Georgetown University Hospital, Washington, D.C.,
5Astellas Pharma US, Inc., Deerfield, Ill., USA

Tóm tắt

<i>Background:</i> Most cases of hyponatremia – serum sodium concentration ([Na<sup>+</sup>]) <135 mEq/l (<135 m<i>M</i>) – are associated with an elevated plasma arginine vasopressin level. This study investigated the efficacy and tolerability of intravenous conivaptan (YM087), a vasopressin V<sub>1A</sub>/V<sub>2</sub>-receptor antagonist, in treating euvolemic and hypervolemic hyponatremia. <i>Methods:</i> Eighty-four hospitalized patients with euvolemic or hypervolemic hyponatremia (serum [Na<sup>+</sup>] 115 to <130 mEq/l) were randomly assigned to receive intravenous placebo or conivaptan administered as a 30-min, 20-mg loading dose followed by a 96-hour infusion of either 40 or 80 mg/day. The primary efficacy measure was change in serum [Na<sup>+</sup>], measured by the baseline-adjusted area under the [Na<sup>+</sup>]-time curve. The secondary measures included time from first dose to a confirmed ≧4 mEq/l serum [Na<sup>+</sup>] increase, total time patients had serum [Na<sup>+</sup>] ≧4 mEq/l higher than baseline, change in serum [Na<sup>+</sup>] from baseline to the end of treatment, and number of patients with a confirmed ≧6 mEq/l increase in serum [Na<sup>+</sup>] or normal [Na<sup>+</sup>] (≧135 mEq/l). <i>Results:</i> Both conivaptan doses increased area under the [Na<sup>+</sup>]-time curve during the 4-day treatment (p < 0.0001 vs. placebo). From baseline to the end of treatment, the least-squares mean ± standard error serum [Na<sup>+</sup>] increase associated with placebo was 0.8 ± 0.8 mEq/l; with conivaptan 40 mg/day, 6.3 ± 0.7 mEq/l; and with conivaptan 80 mg/day, 9.4 ± 0.8 mEq/l. Conivaptan significantly improved all secondary efficacy measures (p < 0.001 vs. placebo, both doses). Conivaptan was generally well tolerated, although infusion-site reactions led to the withdrawal of 1 (3%) and 4 (15%) of patients given conivaptan 40 and 80 mg/day, respectively. <i>Conclusion:</i> Among patients with euvolemic or hypervolemic hyponatremia, 4-day intravenous infusion of conivaptan 40 mg/day significantly increased serum [Na<sup>+</sup>] and was well tolerated.

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American Journal of Nephrology

Tập 27 Số 5

447-457

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