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


METHODS
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.


METHODS
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.
Department of Medicine, Georgetown University, Washington, DC, USA. verbalis@georgetown.edu
Joseph G
JG
Verbalis
David
D
Zeltser
Neila
N
Smith
Abhijit
A
Barve
Masakazu
M
Andoh
D000368:Aged; D000369:Aged, 80 and over; D001552:Benzazepines / Q000008:administration & dosage* / Q000009:adverse effects*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006727:Hormone Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007010:Hyponatremia / Q000097:blood / Q000188:drug therapy*; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012964:Sodium / Q000097:blood; D016896:Treatment Outcome
D001552:Benzazepines; D006727:Hormone Antagonists; D010919:Placebos; C106389:conivaptan; D012964:Sodium