Assessment of the efficacy and safety of intravenous conivaptan in patients with euvolaemic hyponatraemia: subgroup analysis of a randomized, controlled study

Abstract

Objective and design: Most cases of euvolaemic hyponatraemia are associated with elevated plasma levels of AVP. Conivaptan is a high-affinity, nonpeptide vasopressin V(1A)/V(2)-receptor antagonist. We performed a subgroup analysis of a multicentre, randomized, placebo-controlled, double-blind, parallel-group study to evaluate the efficacy and safety of intravenous (i.v.) conivaptan for the treatment of euvolaemic hyponatraemia.

Patients: Fifty-six euvolaemic patients with serum [Na(+)] of 115 to < 130 mmol/l received conivaptan 40 or 80 mg/day or placebo via continuous i.v. infusion for 4 days. A 20-mg loading dose was administered intravenously over 30 min in the conivaptan groups; the placebo group received a placebo loading dose.

Measurements: Change in serum [Na(+)], measured by the baseline-adjusted area under the serum [Na(+)]-time curve (AUC), was the primary efficacy parameter. Secondary efficacy measures included the time from the first dose to a confirmed > or = 4 mmol/l increase in serum [Na(+)], total time with serum [Na(+)] > or = 4 mmol/l above baseline, change in serum [Na(+)] from baseline, and number of patients with a confirmed > or = 6 mmol/l increase in serum [Na(+)] or normal [Na(+)]. Safety assessments included adverse events (AE), incidence of overly rapid correction of serum [Na(+)], and changes in vital signs and electrocardiographic and clinical laboratory parameters.

Results: During the first 2 days of treatment, and over the entire 4-day treatment period, both conivaptan doses significantly increased the serum [Na(+)] AUC more than placebo (P < 0.01). Conivaptan 40 and 80 mg/day significantly improved all secondary efficacy measures. Conivaptan was generally well tolerated; infusion-site reaction was the most common AE.

Conclusions: In hospitalized patients with euvolaemic hyponatraemia, i.v. conivaptan significantly increased serum [Na(+)] promptly and was well tolerated.