Tolvaptan versus fluid restriction in acutely hospitalised patients with moderate-profound hyponatraemia (TVFR-HypoNa): design and implementation of an open-label randomised trial

Table 1 Dosing protocol for study interventions

DAY	Serum sodium	Prior 24 h sodium increment (mmol/L)	Tolvaptan (TOL) Group	Fluid Restriction (FR) Group	Sodium normalised protocol (both groups)
1	115–130		7.5 mg	1000 mL
2	> 134	Any	➔	➔	1500 mL fluid restriction^a
	≤134	> 8	Nil^b	Nil^b
		5–8	7.5 mg	1000 mL
		0–4	15 mg	750 mL
		< 0	30 mg	500 mL
3	> 134	Any	➔	➔	1500 mL fluid restriction^a
	≤134	> 8	Nil^b	Nil^b
		5–8	Same as D2	Same as D2
		0–4	Dose increment^c	FR increment^c
		< 0	Dose increment^c	FR increment^c
4	Usual care after morning blood test including repeat serum sodium 30 days after discharge.

^aAll participants regardless of group assignment with Na > 134 mmol/L on day 2 or on day 3 will receive a 1500-mL fluid restriction that day and no other intervention unless the Na increment was > 8 mmol/L over the preceding 24 h in which case they will not receive fluid restriction or tolvaptan
^bParticipants with Na increment > 8 mmol/L over the preceding 24 h will not receive a fluid restriction or tolvaptan for that day, regardless of group assignment
^cStepwise dose/fluid restriction increments:
• Tolvaptan: 7.5 mg ➔ 15 mg ➔ 30 mg ➔ 60 mg
• Fluid restriction: 1000 mL ➔ 750 mL ➔ 500 mL ➔ 0 mL

ISSN: 1745-6215