DESMOPRESSIN ACETATE TRIHYDRATE for Severe hyponatremia

Stratification factors

• Presence of neurological symptoms at inclusion
• Presence/absence of risk factors for central pontine myelinolysis (chronic alcohol abuse, malnutrition, serum potassium < 3.0 mmol/L)

Inclusion criteria

• {"criterion_text":"- Adults (≥ 18 years)\n- Current admission in ICU\n- Severe hyponatremia defined by SNa < 120 mmol/L in the presence of neurological symptoms (seizures, stupor defined as GCS < 12, or signs of brain herniation) or by SNa < 115 mmol/L\n- Normal or decreased extracellular fluid volume"}

Exclusion criteria

• {"criterion_text":"- Obvious increase of extracellular fluid volume (cirrhosis with ascites, congestive heart failure, nephrotic syndrome)\n- Recent neurosurgery or traumatic brain injury\n- Previous DDAVP or hypertonic fluid administration for the current episode of severe hyponatremia\n- SNa increased by 5 mmol or more between admission at hospital and randomisation (H0)\n- Known contraindication to DDAVP : Allergy; Syndrome of inappropriate antidiuretic hormone secretion (SIADH) ; History of unstable angina and/or known or suspected heart failure ;\tWillebrand disease type IIB\n- Enrolment to another interventional study (clinical trial on medicinal product, medical device and interventional research involving human participants not concerning health product)\n- Pregnancy or breastfeeding\n- Subject deprived of freedom, subject under a legal protective measure\n- No affiliation to any health insurance system\n- Refusal to participate to the study (patient or legal representative or family member or close relative if present)\n- Severe previous neurologic disability (Glasgow Outcome Scale: GOS < 3)\n- Diabetes insipidus receiving DDAVP treatment\n- Moribund state (patient likely to die within 24h)\n- Need for invasive mechanic ventilation\n- Hyponatremia caused by hyperglycaemia (> 30 mmol/L) or hypertriglyceridemia (10 g/L) or hyperproteinaemia (120 g/L)\n- Severe acute kidney injury (KDIGO 3)\n- Severe chronic kidney disease (eGFR <20 ml/min)\n- Coronary patients well stabilized with trinitrine-based medicines"}

Primary endpoints

• {"endpoint_text":"- Proportion of patients with SNa level overcorrection at any time during the first 48h after randomization.","definition_or_measurement_approach":"Proportion of patients experiencing SNa overcorrection during first 48 hours after randomization; measured by serum sodium (SNa) values collected up to 48h post-randomization."}
• {"endpoint_text":"- SNa overcorrection is defined according to presence or absence of risk factors at the time of randomization (chronic alcohol abuse, malnutrition, thiazides or antidepressant medicines, serum potassium<3.0mmol/L, glycaemia>20mmol/L) for CPM: • Patients with any risk factor: SNa increase>6.0 mmol/L in less than 24h, or a SNa increase>12.0 mmol/L in less than 48h. • Patients without risk factor: SNa increase>10.0mmol/L in less than 24h, or a SNa increase>18.0 mmol/L in less than 48h.","definition_or_measurement_approach":"Provides the numerical thresholds used to define 'SNa overcorrection' based on presence/absence of predefined risk factors; measurement uses serial SNa at specified timepoints (H0, H24, H48)."}

Secondary endpoints

• {"endpoint_text":"- Proportion of patients with neurological symptoms at inclusion and who subsequently have a normal Glasgow Coma Scale at H6","definition_or_measurement_approach":"Proportion measured by Glasgow Coma Scale at H6 among those with neurological symptoms at inclusion."}
• {"endpoint_text":"- Length of ICU and hospital stay","definition_or_measurement_approach":"Measured as duration (days) of ICU stay and total hospital stay from inclusion to discharge."}
• {"endpoint_text":"- Time to death after inclusion","definition_or_measurement_approach":"Measured as time from inclusion to death (days)."}
• {"endpoint_text":"- Proportion of patients with the occurrence of central pontine myelinolysis diagnosed on clinical and MRI criteria at day 15 (or earlier if clinically justified)","definition_or_measurement_approach":"Occurrence assessed by clinical evaluation and brain MRI at day 15 (or earlier if justified)."}
• {"endpoint_text":"- Proportion of patients with any (pontine or extrapontine), symptomatic or not, osmotic demyelination as assessed by brain MRI at day 15 (or earlier if clinically justified)","definition_or_measurement_approach":"Assessed by brain MRI at day 15 (or earlier if clinically indicated); includes symptomatic and asymptomatic demyelination."}
• {"endpoint_text":"- Proportion of patients with neurological symptoms with an increase of 5.0 mmol/L or more of SNa from inclusion to H6","definition_or_measurement_approach":"Measured change in SNa from inclusion to H6; proportion meeting ≥5.0 mmol/L increase among those with neurological symptoms."}
• {"endpoint_text":"- Urine output between (i) H0 and H6, (ii) H6 and H12, (iii) H12 and H24, and (iv) H24 and H48","definition_or_measurement_approach":"Urine output volumes recorded in specified intervals (H0-H6, H6-H12, H12-H24, H24-H48)."}
• {"endpoint_text":"- Urine osmolality between (i) H0 and H6, (ii) H6 and H12, (iii) H12 and H24, and (iv) H24 and H48","definition_or_measurement_approach":"Urine osmolality measured at the specified intervals H0-H6, H6-H12, H12-H24, H24-H48."}
• {"endpoint_text":"- Slope of the SNa increase between (i) H0 and H24 and (ii) H0 and H48","definition_or_measurement_approach":"Calculated slope (rate) of SNa change between baseline and H24, and baseline and H48."}
• {"endpoint_text":"- Maximum change of SNa from baseline between (i) H0 and H24 and (ii) H0 and H48","definition_or_measurement_approach":"Maximum absolute change in SNa from baseline to H24 and to H48."}
• {"endpoint_text":"- Total amount of intravenous hypotonic fluids administered between (i) H0 and H24 and (ii) H24 and H48","definition_or_measurement_approach":"Volume (ml) of IV hypotonic fluids administered during H0-H24 and H24-H48 intervals."}
• {"endpoint_text":"- Total amount of sodium and potassium administered between (i) H0 and H24 and (ii) H24 and H48","definition_or_measurement_approach":"Amounts (mmol or g as recorded) of sodium and potassium administered during specified intervals."}
• {"endpoint_text":"- Proportion of patients with seizures, stupor or sign of brain herniation appearing or reappearing after inclusion","definition_or_measurement_approach":"Proportion based on clinical assessments post-inclusion for specified neurological events."}
• {"endpoint_text":"- Occurrence of a reduction of SNa of 5.0 mmol/L or more from inclusion between H0 and H48","definition_or_measurement_approach":"Measured reduction in SNa between inclusion and H48; proportion with decrease ≥5.0 mmol/L."}

Methods

• Recruitment of eligible adult patients currently admitted to ICU at participating hospital/clinic sites in France (screening by ICU staff at participating sites).

France

Earliest CTIS Part Ii Submission Date

15-02-2024

Latest Decision Or Authorization Date

24-10-2025

Processing Time Days

617

Number Of Sites

24

Number Of Participants

260

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France