Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
Department of Endocrinology, The Austin Hospital, Melbourne, Victoria, Australia.
Trials. 2022 Apr 21;23(1):335. doi: 10.1186/s13063-022-06237-5.
Current hyponatraemia guidelines are divided on the use of tolvaptan in hospitalised patients with moderate to severe hyponatraemia, due to an uncertain risk-benefit ratio. We will conduct a randomised trial to test the hypothesis that early use of tolvaptan improves the rate of serum sodium correction and clinical outcomes compared with current standard first-line therapy, restriction of fluid intake, without increasing the risk of serum sodium overcorrection.
We will enrol hospitalised patients with euvolaemic or hypervolaemic hyponatraemia and serum sodium of 115-130 mmol/L at Austin Health, a tertiary care centre in Melbourne, Australia. Participants will be randomised 1:1 to receive either tolvaptan (initial dose 7.5 mg) or fluid restriction (initial limit 1000 ml per 24 h), with titration of therapy based on serum sodium response according to a pre-determined protocol over a 72-h intervention period. The primary endpoint will be the between-group change in serum sodium over time, from study day 1 to day 4. Secondary endpoints include serum sodium increment in the first 24 and 48 h, proportion of participants with normalised serum sodium, length of hospital stay, requirement for serum sodium re-lowering with intravenous dextrose or desmopressin, cognitive and functional measures (Confusion Assessment Method Short form, Timed Up and Go test, hyponatraemia symptom questionnaire), 30-day readmission rate, treatment satisfaction score and serum sodium 30 days after discharge. The trial will be overseen by an independent Data Safety Monitoring Board. Serum sodium will be monitored every 6-12 h throughout the study period, with pre-specified thresholds for commencing intravenous 5% dextrose if serum sodium rise targets are exceeded.
We seek to inform future international guidelines with high-quality data regarding the utility and safety of tolvaptan compared to standard therapy fluid restriction in patients with moderate-severe hyponatraemia in hospital. If tolvaptan use in this patient group is endorsed by our findings, we will have established an evidence-based framework for tolvaptan initiation and monitoring to guide its use.
Australia and New Zealand Clinical Trials Registry ACTRN12619001683123 . Registered on December 2 2019.
目前，由于不确定的风险效益比，低钠血症指南在住院伴有中重度低钠血症的患者中是否使用托伐普坦存在分歧。我们将进行一项随机试验，以检验以下假设：与目前的一线标准治疗（即限制液体摄入）相比，早期使用托伐普坦可提高血清钠纠正率和临床结局，且不会增加血清钠过度纠正的风险。
我们将在澳大利亚墨尔本的三级医疗中心 Austin Health 招募血清钠为 115-130mmol/L 的等容性或高容性低钠血症且住院的患者。参与者将按照 1:1 的比例随机分配至托伐普坦组（初始剂量为 7.5mg）或液体限制组（初始限制为 24 小时内 1000ml），根据预先确定的方案，根据血清钠反应滴定治疗，干预期为 72 小时。主要终点为研究第 1 天至第 4 天期间两组间的血清钠随时间的变化。次要终点包括前 24 小时和前 48 小时的血清钠增加量、血清钠正常化的参与者比例、住院时间、需要静脉滴注葡萄糖或去氨加压素来降低血清钠、认知和功能测量（意识模糊评估方法短表、计时起立行走测试、低钠血症症状问卷）、30 天再入院率、治疗满意度评分以及出院后 30 天的血清钠水平。该试验将由一个独立的数据安全监测委员会监督。在整个研究期间，每隔 6-12 小时监测血清钠，若血清钠升高目标超过预定义阈值，则开始静脉滴注 5%葡萄糖。
我们旨在为国际指南提供高质量的数据，以了解与标准治疗（即液体限制）相比，托伐普坦在住院伴有中重度低钠血症的患者中的效用和安全性。如果我们的研究结果支持托伐普坦在该患者群体中的应用，我们将为托伐普坦的启动和监测建立一个基于证据的框架，以指导其使用。
澳大利亚和新西兰临床试验注册中心 ACTRN12619001683123。于 2019 年 12 月 2 日注册。
