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

Context: 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. Objective: 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. Design: The study design was a 5-d placebo-controlled, randomized, double-blind study. Setting: The study was performed at a hospital. Intervention: Oral conivaptan (40 or 80 mg/d) or placebo was given in two divided doses. Patients: Seventy-four patients (average baseline serum [Na+], 115 to < 130 mEq/liter) were studied. Main Outcome Measure: The main outcome measure was the change from baseline in serum [Na+] area under the curve. Results: 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. Conclusion: Oral conivaptan (40 and 80 mg/d) was well tolerated and efficacious in correcting serum [Na+] in hyponatremia.