Intravenous conivaptan: Effects on the QTc interval and other electrocardiographic parameters in healthy volunteers

Abstract

Prolongation of the QT interval is clinically important because it may be associated with torsade de pointes, a potentially fatal arrhythmia. The objective of this study was to define the effects on electrocardiogram (ECG) of intravenous conivaptan, the first arginine vasopressin V_1A/V₂-receptor antagonist indicated for the treatment of euvolemic hyponatremia, on hospitalized patients without congestive heart failure. After a placebo run-in period, participants in this randomized, single-blind, placebo- and positive-controlled, parallel-group study received an intravenous 20-mg loading dose of conivaptan (day 1), followed by a 40-mg/d continuous infusion (days 1–4); a 20-mg loading dose of conivaptan (day 1), followed by an 80-mg/d continuous infusion (days 1–4); or moxifloxacin 400 mg (positive control) or placebo from day 1 to day 4. The primary ECG endpoint was QTc interval duration, which was determined by the individually corrected QT interval for each subset; secondary endpoints included QT intervals corrected with Bazett’s formula and Fridericia’s formula. No clinically notable changes in ECG parameters were associated with conivaptan, suggesting that conivaptan did not affect cardiac repolarization or cardiac conduction.