SGLT2 抑制剂 Empagliflozin 对等容性和高血容量性低钠血症患者的影响 (EMPOWER)
SGLT2 抑制剂恩格列净对血容量正常和血容量过高的低钠血症患者的影响 - 一项多中心随机双盲安慰剂对照试验（EMPOWER 研究）
Hyponatremia is the most common electrolyte derangement occurring in hospitalized patients. It is usually classified as hypovolemic, euvolemic or hypervolemic. The most common aetiology of euvolemic hyponatremia is the syndrome of inappropriate antidiuresis (SIAD). Hypervolemic hyponatremia is common in patients with congestive heart failure (CHF) (10-27%) and liver cirrhosis (up to approximately 50%). In SIAD, the regulation of arginine vasopressin (AVP) secretion is impaired which leads to free water retention. In CHF and liver cirrhosis, the effective arterial blood volume is decreased leading to non-osmotic baroreceptor mediated AVP release and consecutive free water retention.
Current treatments of euvolemic and hypervolemic hyponatremia, including the most used treatment fluid restriction, are of limited efficacy. Sodium-Glucose-Co-Transporter 2 (SGLT2) inhibitors reduce glucose reabsorption in the proximal tubule, resulting in glucosuria and consecutive osmotic diuresis. A placebo-controlled randomized trial of our group has shown that a short-term, i.e. a 4-days administration of the SGLT2 inhibitor empagliflozin (Jardiance)® in addition to fluid restriction was effective in increasing the serum sodium concentration in 87 patients with SIAD-induced hyponatremia. The effect of empagliflozin (Jardiance)® without additional fluid restriction is however not yet known. Large randomized controlled trials have shown that SGLT2 inhibitors reduced hospitalization for heart failure in patients with, and more recently without type 2 diabetes. No studies have investigated the effect of SGLT2 inhibitors in hypervolemic hyponatremia.
To evaluate the effect of empagliflozin (Jardiance)® in eu- and hypervolemic hyponatremia, a randomized placebo-controlled study is needed.
研究概览
研究类型
注册 (实际的)
阶段
- 第四阶段
联系人和位置
学习地点
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Würzburg、德国、97080
- University Hospital of Würzburg, med. Poliklinik
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Basel、瑞士、4031
- University Hospital Basel
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Biel、瑞士、2502
- Spitalzentrum Biel
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Canton of Lucerne
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Lucerne、Canton of Lucerne、瑞士、6000
- Kantonsspital Luzern
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Canton of Vaud
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Lausanne、Canton of Vaud、瑞士、1011
- Centre Hospitalier Universitaire Vaudois (CHUV)
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Rotterdam、荷兰、3015
- Erasmus Universität Medisch Centrum Rotterdam, Department of Internal Medicine
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- chronic eu- OR hypervolemic non hyperosmolar (<300 mOsm/kg) hyponatremia (heparin plasma sodium <135 mmol/L on day of inclusion)
Exclusion Criteria:
- known hypersensitivity or allergy to class of drugs or the investigational product,
- severe symptomatic hyponatremia in need of treatment with 3% NaCl-solution or in need of intensive/intermediate care treatment at time of inclusion
- clinical hypovolemia
- Severe reduction of eGFR <20 mL/min/1,73 m2 (KDIGO G4 and G5) or end stage renal disease
- Chronic liver insufficiency with Child Pugh Score ≥10 or decompensated liver cirrhosis (jaundice, hepatorenal syndrome, encephalopathy, bleeding, …)
- Hepatic impairment defined as aspartate transaminase (AST) or alanine transaminase (ALT) >3x the upper limit of normal (ULN); or total bilirubin >2x ULN at time of enrolment
- uncontrolled hypothyroidism
- uncontrolled adrenal insufficiency
- systolic blood pressure <90mmHg
- contraindication for lowering blood pressure
- diabetes mellitus type 1 or pancreatic diabetes mellitus
- treatment with SGLT2 inhibitors, lithium chloride, vaptans, demeclocycline or urea on inclusion day
- severe immunosuppression (leucocytes <2 G/l)
- peripheral arterial disease stage III-IV of the Fontaine Classification
- fasting or other reasons preventing medication intake
- previous enrolment into the current study
- participation in another intervention study
- pregnancy, breastfeeding, intention to become pregnant during the course of the study or lack of safe contraception.
- end of life care
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：四人间
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：Empagliflozin
Empagliflozin (Jardiance)® 25mg per os once daily for 30 days |
Empagliflozin 25mg per os once daily for 30 days |
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安慰剂比较：Placebo
Placebo (Lactose tablet) per os once daily for 30 days |
Placebo per os once daily for 30 days |
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Change in average daily area under curve (AUC) for serum sodium concentration
大体时间：4 days
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Change in average daily AUC for serum sodium concentration |
4 days
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Long-term serum sodium change (before/after treatment)
大体时间：30 days
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Absolute change in serum sodium concentration from baseline to end of treatment |
30 days
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Impact intervention on bodyweight
大体时间：30 days
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change of bodyweight |
30 days
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Impact intervention on blood pressure
大体时间：30 days
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change of blood pressure |
30 days
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Course of serum sodium level
大体时间：30 days
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Course of serum sodium level |
30 days
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Change of plasma osmolality
大体时间：30 days
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Change of plasma osmolality |
30 days
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Change of urinary osmolality
大体时间：30 days
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Change of urinary osmolality |
30 days
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Change of plasma urea
大体时间：30 days
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Change of plasma urea |
30 days
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Change of urinary urea
大体时间：30 days
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Change of urinary urea |
30 days
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Change of plasma uric acid
大体时间：30 days
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Change of plasma uric acid |
30 days
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Change of urinary uric acid
大体时间：30 days
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Change of urinary uric acid |
30 days
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Change of plasma creatinin
大体时间：30 days
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Change of plasma creatinin |
30 days
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Change of urinary creatinin
大体时间：30 days
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Change of urinary creatinin |
30 days
|
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Change of plasma potassium
大体时间：30 days
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Change of plasma potassium |
30 days
|
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Change of urinary potassium
大体时间：30 days
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Change of urinary potassium |
30 days
|
|
Change in plasma copeptin
大体时间：30 days
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Change in plasma copeptin |
30 days
|
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Change in plasma aldosterone
大体时间：30 days
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Change in plasma aldosterone |
30 days
|
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Change in plasma renin
大体时间：30 days
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Change in plasma renin |
30 days
|
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Change in plasma MR-proANP
大体时间：30 days
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Change in plasma MR-proANP |
30 days
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Change in plasma NT-proBNP
大体时间：30 days
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Change in plasma NT-proBNP |
30 days
|
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Change in plasma CTX
大体时间：30 days
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Change in plasma CTX |
30 days
|
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Change in plasma P1NP
大体时间：30 days
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Change in plasma P1NP |
30 days
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Occurence of thirst
大体时间：30 days
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Occurence of thirst |
30 days
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Occurence of headache
大体时间：30 days
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Occurence of headache |
30 days
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Occurence of vertigo
大体时间：30 days
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Occurence of vertigo |
30 days
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Occurence of nausea
大体时间：30 days
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Occurence of nausea |
30 days
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Change in general well-being
大体时间：30 days
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Change in general well-being according to visual analogue scale |
30 days
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Change in quality of life
大体时间：30 days
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change in quality of life according to EQ-5D-5L questionnaire |
30 days
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Change in cognitive impairment
大体时间：30 days
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Change in cognitive impairment measured with the MoCa test |
30 days
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Change in visual attention
大体时间：30 days
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Change in visual attention measured with the trail making test |
30 days
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Change in neuromuscular impairment
大体时间：30 days
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Change in neuromuscular impairment measured with the timed up and go test |
30 days
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Change in grip strength
大体时间：30 days
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Change in grip strength measured with a hand dynamometer |
30 days
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Occurence of falls
大体时间：30 days
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Occurence of falls |
30 days
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Occurence of fractures
大体时间：30 days
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Occurence of fractures |
30 days
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Length of hospital stay
大体时间：30 days
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Length of hospital stay |
30 days
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合作者和调查者
调查人员
- 首席研究员：Julie Refardt, MD、University Hospital, Basel, Switzerland
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- EMPOWER study
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
药物和器械信息、研究文件
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