Efficacy and safety of oral conivaptan: a V1A/V2 vasopressin receptor antagonist, assessed in a randomized, placebo-controlled trial in patients with euvolemic or hypervolemic hyponatremia.

Hyponatremia [serum sodium concentration ([Na(+)]), <135 mEq/liter] is the most common fluid and electrolyte abnormality among hospitalized patients. It is frequently caused by the inappropriate release of arginine vasopressin. The objective of this study was to evaluate the efficacy and safety of oral conivaptan, a vasopressin V(1A)/V(2) receptor antagonist, in patients with euvolemic or hypervolemic hyponatremia. The study design was a 5-d placebo-controlled, randomized, double-blind study. The study was performed at a hospital. Intervention: Oral conivaptan (40 or 80 mg/d) or placebo was given in two divided doses. Seventy-four patients (average baseline serum [Na(+)], 115 to <130 mEq/liter) were studied. The main outcome measure was the change from baseline in serum [Na(+)] area under the curve. The least-squares mean change from baseline in the serum [Na(+)] area under the curve with conivaptan (40 and 80 mg/d) was 2.0-fold (P = 0.03) and 2.5-fold (P < 0.001) greater, respectively, than that with placebo. The median time to achieve a confirmed increase in serum [Na(+)] of 4 mEq/liter or more from baseline was 71.7 h for placebo, 27.5 h for 40 mg/d conivaptan (P = 0.044), and 12.1 h for 80 mg/d conivaptan (P = 0.002). The mean total times during which patients had a serum [Na(+)] level of 4 mEq/liter or more above baseline were 46.5, 69.8, and 88.8 h (P = 0.001), respectively. The least-squares mean change in serum [Na(+)] from baseline to end of treatment was 3.4 mEq/liter for placebo, 6.4 mEq/liter for 40 mg/d conivaptan, and 8.2 mEq/liter for 80 mg/d conivaptan (P = 0.002). A confirmed normal serum [Na(+)] (>/=135 mEq/liter) or increase of 6 mEq/liter or more was observed in 48% of patients given placebo, 71% given 40 mg/d conivaptan, and 82% given 80 mg/d conivaptan (P = 0.014). Headache, hypotension, nausea, constipation, and postural hypotension were the most common adverse events. Oral conivaptan (40 and 80 mg/d) was well tolerated and efficacious in correcting serum [Na(+)] in hyponatremia.

Citation

Jalal K Ghali, Michael J Koren, James R Taylor, Esther Brooks-Asplund, Kaisheng Fan, Walker A Long, Neila Smith. Efficacy and safety of oral conivaptan: a V1A/V2 vasopressin receptor antagonist, assessed in a randomized, placebo-controlled trial in patients with euvolemic or hypervolemic hyponatremia. The Journal of clinical endocrinology and metabolism. 2006 Jun;91(6):2145-52

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PMID: 16522696

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