循環血液量減少症および循環血液量増加性低ナトリウム血症患者における SGLT2 阻害剤エンパグリフロジンの効果 (EMPOWER)
循環血液量減少症および循環血液量亢進性低ナトリウム血症患者における SGLT2 阻害剤エンパグリフロジンの効果 - 多施設ランダム化二重盲検プラセボ対照試験 (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.
調査の概要
研究の種類
入学 (実際)
段階
- フェーズ 4
連絡先と場所
研究場所
-
-
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Rotterdam、オランダ、3015
- Erasmus Universität Medisch Centrum Rotterdam, Department of Internal Medicine
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Basel、スイス、4031
- University Hospital Basel
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Biel、スイス、2502
- Spitalzentrum Biel
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Canton of Lucerne
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Lucerne、Canton of Lucerne、スイス、6000
- Kantonsspital Luzern
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Canton of Vaud
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Lausanne、Canton of Vaud、スイス、1011
- Centre Hospitalier Universitaire Vaudois (CHUV)
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Würzburg、ドイツ、97080
- University Hospital of Würzburg, med. Poliklinik
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-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Empagliflozin
Empagliflozin (Jardiance)® 25mg per os once daily for 30 days |
Empagliflozin 25mg per os once daily for 30 days |
|
プラセボコンパレーター：Placebo
Placebo (Lactose tablet) per os once daily for 30 days |
Placebo per os once daily for 30 days |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in average daily area under curve (AUC) for serum sodium concentration
時間枠：4 days
|
Change in average daily AUC for serum sodium concentration |
4 days
|
|
Long-term serum sodium change (before/after treatment)
時間枠：30 days
|
Absolute change in serum sodium concentration from baseline to end of treatment |
30 days
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Impact intervention on bodyweight
時間枠：30 days
|
change of bodyweight |
30 days
|
|
Impact intervention on blood pressure
時間枠：30 days
|
change of blood pressure |
30 days
|
|
Course of serum sodium level
時間枠：30 days
|
Course of serum sodium level |
30 days
|
|
Change of plasma osmolality
時間枠：30 days
|
Change of plasma osmolality |
30 days
|
|
Change of urinary osmolality
時間枠：30 days
|
Change of urinary osmolality |
30 days
|
|
Change of plasma urea
時間枠：30 days
|
Change of plasma urea |
30 days
|
|
Change of urinary urea
時間枠：30 days
|
Change of urinary urea |
30 days
|
|
Change of plasma uric acid
時間枠：30 days
|
Change of plasma uric acid |
30 days
|
|
Change of urinary uric acid
時間枠：30 days
|
Change of urinary uric acid |
30 days
|
|
Change of plasma creatinin
時間枠：30 days
|
Change of plasma creatinin |
30 days
|
|
Change of urinary creatinin
時間枠：30 days
|
Change of urinary creatinin |
30 days
|
|
Change of plasma potassium
時間枠：30 days
|
Change of plasma potassium |
30 days
|
|
Change of urinary potassium
時間枠：30 days
|
Change of urinary potassium |
30 days
|
|
Change in plasma copeptin
時間枠：30 days
|
Change in plasma copeptin |
30 days
|
|
Change in plasma aldosterone
時間枠：30 days
|
Change in plasma aldosterone |
30 days
|
|
Change in plasma renin
時間枠：30 days
|
Change in plasma renin |
30 days
|
|
Change in plasma MR-proANP
時間枠：30 days
|
Change in plasma MR-proANP |
30 days
|
|
Change in plasma NT-proBNP
時間枠：30 days
|
Change in plasma NT-proBNP |
30 days
|
|
Change in plasma CTX
時間枠：30 days
|
Change in plasma CTX |
30 days
|
|
Change in plasma P1NP
時間枠：30 days
|
Change in plasma P1NP |
30 days
|
|
Occurence of thirst
時間枠：30 days
|
Occurence of thirst |
30 days
|
|
Occurence of headache
時間枠：30 days
|
Occurence of headache |
30 days
|
|
Occurence of vertigo
時間枠：30 days
|
Occurence of vertigo |
30 days
|
|
Occurence of nausea
時間枠：30 days
|
Occurence of nausea |
30 days
|
|
Change in general well-being
時間枠：30 days
|
Change in general well-being according to visual analogue scale |
30 days
|
|
Change in quality of life
時間枠：30 days
|
change in quality of life according to EQ-5D-5L questionnaire |
30 days
|
|
Change in cognitive impairment
時間枠：30 days
|
Change in cognitive impairment measured with the MoCa test |
30 days
|
|
Change in visual attention
時間枠：30 days
|
Change in visual attention measured with the trail making test |
30 days
|
|
Change in neuromuscular impairment
時間枠：30 days
|
Change in neuromuscular impairment measured with the timed up and go test |
30 days
|
|
Change in grip strength
時間枠：30 days
|
Change in grip strength measured with a hand dynamometer |
30 days
|
|
Occurence of falls
時間枠：30 days
|
Occurence of falls |
30 days
|
|
Occurence of fractures
時間枠：30 days
|
Occurence of fractures |
30 days
|
|
Length of hospital stay
時間枠：30 days
|
Length of hospital stay |
30 days
|
協力者と研究者
捜査官
- 主任研究者：Julie Refardt, MD、University Hospital, Basel, Switzerland
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- EMPOWER study
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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