empagliflozin for Hyponatremia

Inclusion criteria

• {"criterion_text":"- Adult patients, aged ≥18 years"}
• {"criterion_text":"- Chronic eu- OR hypervolemic non hyperosmolar (<300 mOsm/kg) hyponatremia (heparin plasma sodium <130mmol/L on day of inclusion)"}

Exclusion criteria

• {"criterion_text":"- Known hypersensitivity or allergy to class of drugs or the investigational product"}
• {"criterion_text":"- Contraindication for lowering blood pressure"}
• {"criterion_text":"- Diabetes mellitus type 1 or pancreatic diabetes mellitus"}
• {"criterion_text":"- Treatment with SGLT2 inhibitors, lithium chloride, vaptans, demeclocycline or urea on inclusion day"}
• {"criterion_text":"- Severe immunosuppression (leucocytes <2 G/l)"}
• {"criterion_text":"- Peripheral arterial disease stage III-IV of the Fontaine Classification"}
• {"criterion_text":"- Fasting or other reasons preventing medication intake"}
• {"criterion_text":"- Participation in another intervention study"}
• {"criterion_text":"- Pregnancy, breastfeeding, intention to become pregnant during the course of the study or lack of safe contraception"}
• {"criterion_text":"- End of life care"}
• {"criterion_text":"- Severe symptomatic hyponatremia in need of treatment with 3% NaCl-solution or in need of intensive/intermediate care treatment at time of inclusion"}
• {"criterion_text":"- Clinical hypovolemia"}
• {"criterion_text":"- Severe reduction of eGFR <20 mL/min/1,73 m2 (KDIGO G4 and G5) or end stage renal disease"}
• {"criterion_text":"- Chronic liver insufficiency with Child Pugh Score ≥10 or decompensated liver cirrhosis (jaundice, hepatorenal syndrome, encephalopathy, bleeding, …)"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Uncontrolled hypothyroidism"}
• {"criterion_text":"- Uncontrolled adrenal insufficiency"}
• {"criterion_text":"- Systolic blood pressure <90mmHg"}

Primary endpoints

• {"endpoint_text":"- The short-term outcome is the change in average daily area under the curve (AUC) for plasma sodium concentration from baseline (day 0) to day 4.","definition_or_measurement_approach":"Change in average daily area under the curve (AUC) for plasma sodium concentration from baseline (day 0) to day 4."}
• {"endpoint_text":"- The long-term outcomes is the change in plasma sodium concentration from baseline to day 30","definition_or_measurement_approach":"Change in plasma sodium concentration from baseline to day 30."}

Secondary endpoints

• {"endpoint_text":"- Short (day 1, day 2, day 3, day of discharge term course of plasma sodium level","definition_or_measurement_approach":"Plasma sodium level measured on day 1, day 2, day 3 and day of discharge."}
• {"endpoint_text":"- Urine sodium, eGFR, serum and urine -osmolality, -potassium, -creatinine, -urea, -uric acid, -glucose, -CRP at baseline, on day 4, and day 30","definition_or_measurement_approach":"Laboratory measurements (urine sodium, eGFR, serum and urine osmolality, potassium, creatinine, urea, uric acid, glucose, CRP) at baseline, day 4 and day 30."}
• {"endpoint_text":"- Blood and urine aliquots on day 0, day 1, day 4 and day 30, including predefined analysis: markers of salt-water balance (MR-proANP, NT-proBNP, copeptin, aldosteron, renin) and markers of bone metabolism (procollagen type I N propeptide (P1NP) and serum C telopeptide (CTX)","definition_or_measurement_approach":"Collection of blood and urine aliquots on days 0,1,4,30 with predefined biomarker analyses (MR-proANP, NT-proBNP, copeptin, aldosterone, renin, P1NP, CTX)."}
• {"endpoint_text":"- Daily fluid intake (mL) from baseline (day 0) to day 4","definition_or_measurement_approach":"Daily recorded fluid intake in mL from baseline to day 4."}
• {"endpoint_text":"- Change in body weight (including AUC 24h – 4 days), blood pressure and heart rate twice a day at baseline (day 0) and on day 1 and then once a day on day 2, day 3, day 4, and day 30","definition_or_measurement_approach":"Measurements of body weight, blood pressure and heart rate as specified (twice daily at baseline and day1; once daily on days 2,3,4 and day 30); includes AUC 24h–4 days for weight."}
• {"endpoint_text":"- Course of thirst and symptoms of hyponatremia assessed on a yes or no basis: headache, vertigo and nausea at baseline (day 0), on day 4 and day 30","definition_or_measurement_approach":"Presence/absence (yes/no) of thirst and specific symptoms (headache, vertigo, nausea) at baseline, day 4 and day 30."}
• {"endpoint_text":"- Course of general well-being rated by patients on a visual analogue scale (VAS) reaching from 0 (no well-being) to 10 (excellent well-being) at baseline (day 0), on day 4 and day 30","definition_or_measurement_approach":"Patient-rated VAS (0–10) for general well-being at baseline, day 4 and day 30."}
• {"endpoint_text":"- Change in quality of life assessed by the EQ-5D-5L questionnaire at baseline (day 0), on day 4 and day 30","definition_or_measurement_approach":"EQ-5D-5L questionnaire administered at baseline, day 4 and day 30."}
• {"endpoint_text":"- Change in neurocognitive functions assessed by the MoCA Test and the Trail Making Test A and B at baseline (day 0), on day 4 and day 30","definition_or_measurement_approach":"MoCA and Trail Making Test A and B assessments at baseline, day 4 and day 30 to evaluate neurocognitive function change."}
• {"endpoint_text":"- Change in gait stability assessed by the Timed Up and Go Test at baseline (day 0), on day 4 and day 30","definition_or_measurement_approach":"Timed Up and Go Test at baseline, day 4 and day 30."}
• {"endpoint_text":"- Fall as admission (co)-diagnosis at baseline or as re-admission (co)-diagnosis during treatment period (Day 0 – Day 30)","definition_or_measurement_approach":"Recording of falls as admission co-diagnosis at baseline or as re-admission diagnosis during Day 0–30."}
• {"endpoint_text":"- Incidence of fractures during the twelve months prior to treatment start, fractures as admission (co)-diagnosis at baseline or as re-admission (co)-diagnosis during treatment period (Day 0 – Day 30)","definition_or_measurement_approach":"Assessment of fracture incidence in prior 12 months and fractures as admission or re-admission diagnoses during Day 0–30."}
• {"endpoint_text":"- Grip strength measured with a hand dynamometer at baseline (day0), on day 4 and day 30","definition_or_measurement_approach":"Hand dynamometer measurements at baseline, day 4 and day 30."}
• {"endpoint_text":"- Percentage of patients with plasma sodium concentration that has normalized after 4, on day of discharge) and after 30 days of treatment","definition_or_measurement_approach":"Proportion of patients achieving normalized plasma sodium at day 4, discharge, and day 30."}
• {"endpoint_text":"- Duration (days) until normonatremia has been reached","definition_or_measurement_approach":"Time in days from baseline until normonatremia is achieved."}
• {"endpoint_text":"- Recurrence-rate of hyponatremia during treatment period (Day 0 – Day 30)","definition_or_measurement_approach":"Rate of hyponatremia recurrence during Day 0–30."}
• {"endpoint_text":"- Recurrence of hyponatremia after treatment completion according to plasma sodium measurement at follow up (day 37 +21/- 3 days)","definition_or_measurement_approach":"Plasma sodium measured at follow-up visit (day 37 ± window) to assess recurrence after treatment completion."}
• {"endpoint_text":"- Need for additional hyponatremia treatment and treatment escalation (e.g. administration of 3% NaCl infusion) during treatment period (Day 0 – Day 30)","definition_or_measurement_approach":"Recording need for additional treatments or escalation (e.g., 3% NaCl infusion) during Day 0–30."}
• {"endpoint_text":"- Rate of ICU-admissions during treatment period (Day 0 – Day 30)","definition_or_measurement_approach":"Number/rate of ICU admissions during Day 0–30."}
• {"endpoint_text":"- Length of hospital stay (days)","definition_or_measurement_approach":"Duration of hospital stay in days."}
• {"endpoint_text":"- Rate of readmission due to hyponatremia and other causes during treatment period (Day 0 – Day 30)","definition_or_measurement_approach":"Rate of readmissions for hyponatremia and other causes during Day 0–30."}
• {"endpoint_text":"- Baseline characteristics including age, gender, medical history, medication, date of hospitalisation and admission diagnosis.","definition_or_measurement_approach":"Collection of baseline demographic and clinical characteristics at enrolment."}

Germany

Earliest CTIS Part Ii Submission Date

17-04-2025

Latest Decision Or Authorization Date

03-09-2025

Processing Time Days

139

Number Of Sites

1

Number Of Participants

30

Netherlands

Earliest CTIS Part Ii Submission Date

04-04-2025

Latest Decision Or Authorization Date

03-09-2025

Processing Time Days

152

Number Of Sites

1

Number Of Participants

30

Primary sponsor

Full Name

Universitaetsspital Basel

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Switzerland