None listed
Conditions
Brief summary
Hyponatraemia is common in hospitalised patients. Our Australian data demonstrate that hyponatraemia leads to adverse outcomes and delays hospital discharge, due to unavailability of effective pathophysiology-based treatment. In Australia, fluid restriction is the mainstay of treatment for euvolaemic and hypervolaemic hypotonic hyponatraemia in hospital inpatients. Tolvaptan, a vasopressin V2-receptor antagonist, may be more effective.
Interventions
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 < 135 mmol/L and the increment over the previous 24h is in the range of 5-8 mmol/L, the dose continue at 7.5mg.
- If the serum sodium is < 135 mmol/L and the increment over the prev
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 < 135 mmol/L and the increment over the previous 24h is in the range of 5-8 mmol/L, the dose continue at 7.5mg. - If the serum sodium is < 135 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 < 135 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 < 135 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.
Sponsors
The University of Melbourne
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Acutely hospitalised patients with hypotonic hyponatraemia (serum sodium 115-130 mmol/L) at 0800 hours on day 1 of their hospital admission (day of presentation being day 0).
Exclusion criteria
Hypovolaemia Acute polydipsia (urine specific gravity < 1.003) Severe symptoms warranting hypertonic saline (vomiting, coma (GCS <8), deep somnolence (sedation score >1), seizure, respiratory arrest) Thiazide or thiazide-like diuretic use within preceding 5 days Risk factors for osmotic demyelination syndrome (malnutrition, alcohol abuse, Child-Pugh B or C cirrhosis, potassium < 3.5 mmol/L on day 1, increment in serum sodium from day 0 to day 1 of > 0.5mmol/L/h or > 10 mmol/L). Systolic blood pressure <100mmHg Glucocorticoid deficiency Mineralocorticoid deficiency Overt hypothyroidism Chronic kidney disease stage 5 Inability to drink fluid unaided Pregnancy or breastfeeding Marked hyperglycaemia (Day 1 venous blood gas glucose > 20 mmol/L)
Outcome results
None listed