Tolvaptan versus Urea in acutely hospitalised patients with low blood sodium concentration
A randomised multi-centre trial of Tolvaptan vs. Urea for therapy of hyponatraemia after failure of fluid restriction in hospital inpatients
University of Melbourne
112 participants
Feb 3, 2025
Interventional
Conditions
Summary
Hyponatraemia is common in hospitalised patients. Our Australian data demonstrate that hyponatraemia leads to adverse outcomes and delays hospital discharge. In Australia, fluid restriction is the mainstay of treatment for hypotonic hyponatraemia in hospital inpatients, but it is often ineffective because it does not treat the underlying pathophysiology of hyponatraemia. Tolvaptan, a vasopressin V2-receptor antagonist, and urea are common second-line therapies for hyponatraemia, but it is not known which is more effective.
Eligibility
Inclusion Criteria1
- Acutely hospitalised patients with hypotonic hyponatraemia (serum sodium 115-130 mmol/L) with sodium rise less than or equal to 4 mmol/L per 24 hours at 0800 hours on day 1 of their hospital admission (day of presentation being day 0), despite at least 24 hours of fluid restriction.
Exclusion Criteria11
- Hypovolaemia defined as either clinical impression of hypovolaemia; or urine sodium <20 mmol/L
- Acute polydipsia defined by first collected urine sample specific gravity <1.003
- Severe symptoms warranting hypertonic saline: repeated vomiting on Day 1 of admission, coma (defined by Glasgow Coma Score <8) on Day 1 of admission, deep somnolence (defined by sedation score>1) on Day 1 of admission, seizure at any time during admission, respiratory arrest at any time during admission
- Thiazide or thiazide-like diuretic use within the preceding 5 days
- Risk factors for osmotic demyelination syndrome: malnutrition (BMI <16 or other clinical concern), alcohol abuse (>14 standard drinks per week), child-Pugh B or C cirrhosis, hypokalaemia (K<3.0 mmol/L on Day 1 of admission), increment in serum sodium from baseline to Day 1 of >5mmol/L
- Other endocrine causes of hyponatraemia: untreated glucocorticoid deficiency or mineralocorticoid deficiency, overt hypothyroidism (thyroid stimulating hormone >20)
- Chronic Kidney Disease Stage 5
- Systolic blood pressure <100mmHg
- Inability to drink fluid orally unaided
- Pregnancy (by history, confirmed if necessary by serum beta-hCG) or breastfeeding
- Extreme hyperglycaemia (Day 1 venous blood gas glucose >20mmol/L)
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Interventions
Arm 1: Tolvaptan Tolvaptan will be administered once daily for 3 days in oral tablet form. On day one the dose will be 7.5mg. On day 2 the dose will be titrated according to serum sodium and the serum sodium increment over the previous 24 hours. - If the serum sodium is > 134 mmol/L the dose will be 0mg. - If the serum sodium is less than or equal to 134 mmol/L and the increment over the previous 24h is >8 mmol/L the dose will be 0mg. - If the serum sodium is less than or equal to 134 mmol/L and the increment over the previous 24h is in the range of 5-8 mmol/L, the dose will continue at 7.5mg. - If the serum sodium is less than or equal to 134 mmol/L and the increment over the previous 24h is <5 mmol/L, the dose will be increased to 15mg. On day 3 the dose will be titrated according to serum sodium, the serum sodium increment, over the previous 24 hours, and the dose received on day 2. - If the serum sodium is > 134 mmol/L the dose will be 0mg. - If the serum sodium is less than or equal to 134 mmol/L and the increment over the previous 24h is >8 mmol/L the dose will be 0mg. - If the serum sodium is less than or equal to 134 mmol/L and the increment over the previous 24h is in the range of 5-8 mmol/L, the same dose will be given on day 3 as was given on day 2. - If the serum sodium is less than or equal to 134 mmol/L and the increment over the previous 24h is <5 mmol/L, the dose on day 3 will be increased: 7.5mg if 0mg was given on day 2, 15mg if 7.5mg was given on day 2, or 30mg if 15mg was given on day 2. Tolvaptan will be administered by the ward nursing staff, together with their regular medications (if any). The ward nursing staff will supervise the patient while they are swallowing the tablets, which is in keeping with standard hospital protocol.
Locations(1)
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ACTRN12624000756527