Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2007) 14 OC6.7

ECE2007 Oral Communications Cardiovascular endocrinology (7 abstracts)

Evaluation of tolvaptan, an oral vasopressin V2 receptor antagonist, in ‘asymptomatic’ hyponatremia: effects on sodium concentration and patient reported health outcomes

Peter Gross 1 , Joseph Verbalis 2 , Guy Decaux 4 , John Ouyang 3 , Mary Hobart 3 , Cesare Orlandi 3 & Frank Czerwiec 3

1Universitätsklinikum Carl Gustav Carus, Dresden, Germany; 2Georgetown University, Washington, DC, United States; 3Otsuka Maryland Research Institute, Rockville, MD, United States; 4Erasme University Hospital, Brussels, Belgium; 5For the SALT Study Investigators, in Europe, Canada and the, United States.

Background: Hyponatremia (Na+≤134 mmol/L), the most common electrolyte derangement, is caused by inappropriate vasopressin-mediated water resorption in the kidney. Treating symptomatic hyponatremia is difficult and risky; as difficult as maintaining normal sodium levels. We tested if tolvaptan, an oral vasopressin V2 receptor antagonist, improves hyponatremia and self-reported health outcomes.

Methods: Two multicenter, randomized, double-blind, placebo-controlled trials evaluated tolvaptan in asymptomatic, non-hypovolemic hyponatremia patients. Upon obtaining local Ethics Committee approval and patients’ consent, oral placebo (n=223) or tolvaptan (n=225) was given for 30 days. The first single daily dose (15 mg) was monitored in-hospital with optional fluid restriction. Patients were discharged and fluid intake and study drug (30 or 60 mg) were titrated as clinically indicated. Co-primary endpoints were the average daily area under the curve of serum sodium concentration change from baseline to day 4 and 30. Overall SF-12 Physical (PCS) and Mental Component Summary (MCS) score changes from baseline to day 30 were secondary endpoints. A hyponatremia disease-specific survey (HDS) was also tested.

Results: Serum sodium increased more with tolvaptan than placebo over the first 4 days (P<0.001) and the entire 30-days (P<0.001). On stopping tolvaptan therapy, sodium concentrations fell to placebo levels. The day 30 PCS was unchanged, however the MCS was significantly improved in the tolvaptan group (P=0.02). MCS improvements correlated positively with rise in serum sodium (r=0.2, P=0.001). Tolvaptan differed from placebo in the HDS survey in the moderately severe hyponatremia subjects (<130 mmol/L) in mental concentration, calculation and memory (P<0.05 or better). Side effects associated with tolvaptan included increased thirst, dry mouth, and increased urination.

Conclusions: Tolvaptan, an oral V2 receptor antagonist, effectively increased and maintained serum sodium concentrations in hyponatremic patients. These changes were associated with improved perception of mental/cognitive health.

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