Tolvaptan and Neurocognitive Function in Mild to Moderate Chronic Hyponatremia: A Randomized Trial (INSIGHT)
| Autor: | Joseph G. Verbalis, Howard Ellison, Mary Hobart, Holly Krasa, John Ouyang, Frank S. Czerwiec, Otis Barnum, Karthikeya Devireddy, Miguel Franco, Francis Goldstein, Terrence C. Hack, Kianoosh Kaveh, Ali Khojasteh, John LaFata, Michael J. Lillestol, Sarah Olelewe, David Rosenbaum, Mitchell H. Rosner, Miguel Trevino, Joseph Verbalis, Wayne Wells |
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| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Tolvaptan 030209 endocrinology & metabolism Pilot Projects Placebo Asymptomatic Severity of Illness Index law.invention 03 medical and health sciences 0302 clinical medicine Randomized controlled trial Double-Blind Method law Internal medicine Severity of illness Clinical endpoint Medicine Humans Cognitive Dysfunction 030212 general & internal medicine Aged Aged 80 and over business.industry Benzazepines Middle Aged medicine.disease Nephrology Chronic Disease Physical therapy Female medicine.symptom business Hyponatremia Neurocognitive Antidiuretic Hormone Receptor Antagonists medicine.drug |
| Zdroj: | American journal of kidney diseases : the official journal of the National Kidney Foundation. 67(6) |
| ISSN: | 1523-6838 |
| Popis: | This trial assessed the effect of tolvaptan on cognition, gait, and postural stability in adult patients with mild to moderate asymptomatic hyponatremia.Phase 3b, multicenter, randomized, double-blind, placebo-controlled, parallel-group pilot study.57 men and women 50 years or older with chronic asymptomatic euvolemic or hypervolemic hyponatremia (serum sodium concentration120-135 mEq/L) at 16 sites.Patients were randomly assigned 1:1 to receive tolvaptan or matching placebo beginning at a dose of 15mg/d, with titration to 30 or 60mg/d based on change in serum sodium concentration and tolerance.Primary: change from baseline in the neurocognitive composite score of speed domains. Secondary: changes from baseline in individual neurocognitive domain scores, overall neurocognitive composite score, gait and postural stability test results, and serum sodium concentrations.Mean serum sodium concentration increased from 129 to 136 mEq/L in the tolvaptan group and from 130 to 132 mEq/L in the placebo group (P0.001). There was no difference in overall neurocognitive composite scores of speed domains between groups, except for the psychomotor speed domain, which was statistically improved following hyponatremia correction with tolvaptan (treatment effect, 0.27; 95% CI, 0.04-0.51; P=0.03).There were some imbalances between treatment groups in baseline neurocognitive function scores and some baseline test results were near normal, leaving little opportunity for improvement. Formal sample size calculations were not performed because this was a pilot study. The study population was small (n=57) and treatment was of short duration (3 weeks). The primary end point of the study was not significant; thus, subgroup analyses are subject to errors of multiplicity and should be regarded as hypothesis generating.Tolvaptan was effective in reversing chronic hyponatremia, and this correlated with improvements in results of a variety of neurocognition tests, particularly rapid motor movements, which tended to reverse following return to a low baseline serum sodium concentration after treatment withdrawal. |
| Databáze: | OpenAIRE |
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