Oral Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

Tolvaptan versus fluid restriction in hospital inpatients with moderate-profound hyponatraemia 115-130 mmol/L: An open-label, randomised, clinical trial (#157)

Annabelle M Warren 1 2 3 , Mathis Grossmann 1 2 , Rudolf Hoermann 2 , Jeffrey D Zajac AO 1 2 , Nick Russell 1 2
  1. Department of Endocrinology, The Austin Hospital, Heidelberg, VIC, Australia
  2. Department of Medicine, University of Melbourne, Melbourne, VIC, Australia
  3. Department of Endocrinology, The Alfred Hospital, Melbourne, VIC, Australia

Hyponatraemia is a common electrolyte disorder that can have significant morbidity(1). Current first-line therapy, fluid restriction, is ineffective in around half of cases(2). Tolvaptan is an arginine vasopressin V2-receptor antagonist effective in mild-moderate hyponatraemia(3), however, its efficacy and safety in more significant hyponatraemia has not been assessed in a controlled study(4,5). We hypothesised that tolvaptan would cause greater rise in plasma sodium (pNa), reduce length of stay and improve symptoms, but would require more intervention to prevent overcorrection of pNa.

This investigator-initiated, three-day, randomised, open-label trial was conducted at a single tertiary hospital, Austin Health.  Eligible hospitalised patients with serum sodium 115-130mmol/L were randomly assigned (1:1) to tolvaptan 7.5mg oral daily or fluid restriction (FR) <1000ml/day. Each intervention was titrated per protocol based on pNa response, with pre-specified thresholds for dextrose 5% intervention if targets were exceeded.

Between May 2021 and April 2024, 1782 inpatients with hyponatraemia were electronically screened,131 clinically assessed, and 54 randomised; to tolvaptan (n=28) or FR (n=26). The mean baseline pNa was 123.7mmol/L (tolvaptan) and 123.9mmol/L (FR). Plasma sodium concentration increased more in the tolvaptan group than FR over 3 days (p.overall<0.001)(Fig 1). The mean adjusted difference in pNa between groups at day 3 was 3.5mmol/L (95%CI 1.9-5.2), and day 4 was 2.5mmol/L (95%CI 0.8-4.2) in favour of tolvaptan. Five participants who received tolvaptan (18.5%) required dextrose to prevent or reverse overcorrection. No serious adverse effects attributable to therapy occurred. There was no significant difference in length of stay, pNa 30 days after discharge or symptom scores.

Tolvaptan was superior to FR at raising pNa levels over 3 days, however intervention was required to prevent overcorrection in some, and there were no discernible benefits in length of stay or symptom burden. We offer the first prospectively-validated protocol for monitoring and intervention to prevent tolvaptan-related overcorrection.66aed1343677b-Screen+Shot+2024-08-04+at+10.54.56+am.png

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  5. Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol. 2014;170(3):G1-47.