Systematic Use of DDAVP to Prevent Serum Sodium Overcorrection in Severe Hyponatremia (DASSOH)

Assistance Publique - Hôpitaux de Paris

Status and phase: Enrolling; Phase 3

Conditions: Hyponatremia

Treatments: Drug: DDAVP; Drug: Standard hyponatremia treatment

Study type: Interventional

Funder types: Other

Identifiers

NCT06020495

APHP220676

Details and patient eligibility

About

ICU patients with severe hyponatremia and a high risk of rapid SNa overcorrection.

Full description

Multicentre, prospective, open-label randomized controlled superiority trial with stratification on the presence of neurological symptoms at inclusion and on the presence/absence of risk factors for central pontine myelinolysis (chronic alcohol abuse, malnutrition, serum potassium < 3.0 mmol/L).

Patients in ICU with severe hyponatremia defined by SNa < 115 mmol/L or SNa < 120 mmol/L in the presence of neurological symptoms (convulsions, stupor defined by a Glasgow score <12 or signs of brain herniation) and a normal or decreased extracellular fluid volume will be included.

After written informed consent, they will be randomized (1:1), using a computer-generated randomization scheme of various-sized blocks, stratified by the presence of neurological symptoms at inclusion (seizures, stupor defined as Glasgow score <12 or signs of brain herniation) and on the presence/absence of risk factors for central pontine myelinolysis (chronic alcohol abuse [defined according to World Health Organization definition], malnutrition [BMI<20.5 or weight loss >5% in 3 months], serum potassium < 3.0 mmol/L), through a centralized 24-hour Internet service (CleanWEB™), to receive standard hyponatremic treatment alone or standard hyponatremic treatment and DDAVP 4 μg/ml IV, after randomisation and for a total duration of 48 hours. Since administration of DDAVP leads to an important decrease in urine output and increase in urine osmolarity which are clinically obvious very rapidly, a single or double blind trial is not appropriate. However, all investigators will be unaware of aggregate outcomes during the study and brain MRI imaging will be performed and analyzed blinded to the randomization group

Enrollment: 260 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adults ( ≥18 years)
• Current admission in ICU
• Severe hyponatremia defined by SNa <120 mmol/L in the presence of neurological symptoms (seizures, stupor defined as Glasgow score < 12, or signs of brain herniation) or by SNa <115 mmol/L
• Normal or decreased extracellular fluid volume

Exclusion criteria

• Obvious increase of extracellular fluid volume (cirrhosis with ascites, congestive heart failure, nephrotic syndrome);

• Hyponatremia caused by hyperglycaemia (> 30 mmol/L) or hypertriglyceridemia (10 g/L) or hyperproteinaemia (120 g/L)

• Severe acute kidney injury (KDIGO 3)

• Severe chronic kidney disease (eGFR <20 ml/min)

• Coronary patients well stabilized with trinitrine-based medicines

• Recent neurosurgery or traumatic brain injury

• Previous DDAVP or hypertonic fluid administration for the current episode of severe hyponatremia

• SNa increased by 5 mmol or more between admission at hospital and randomisation (H0)

• Known contraindication to DDAVP

  • Allergy
  • Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
  • History of unstable angina and/or known or suspected heart failure.
  • Willebrand disease type IIB

• Severe previous neurologic disability (Glasgow Outcome Scale: GOS < 3)

• Diabetes insipidus receiving DDAVP treatment

• Moribund state (patient likely to die within 24h)

• Need for invasive mechanic ventilation

• Enrolment to another interventional study (clinical trial on medicinal product, medical device and interventional research involving human participants not concerning health product)

• Pregnancy or breastfeeding

• Subject deprived of freedom, subject under a legal protective measure

• No affiliation to any health insurance system

• Refusal to participate to the study (patient or legal representative or family member or close relative if present)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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260 participants in 2 patient groups

DDAVP

Experimental group

Description:

DDAVP 4µg/ml IV Additional doses may be administrated every 6h for a maximum of 48h - Standard hyponatremia treatment : Presence of neurological symptoms : sodium chloride 3% 150ml for 20 min Absence of neurological symptoms : Hyper or isotonic fluid but never hypotonic

Treatment:

Drug: DDAVP

Standard hyponatremia treatment

Active Comparator group

Description:

Standard hyponatremia treatment alone : Presence of neurological symptoms : sodium chloride 3% 150ml for 20 min Absence of neurological symptoms : Hyper or isotonic fluid but never hypotonic

Treatment:

Drug: Standard hyponatremia treatment