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Recruiting NCT06020495

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

Phase III Interventional Hyponatremia

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: DDAVP, Standard hyponatremia treatment.
Who it may be relevant to
Registry conditions: Hyponatremia. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
France
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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Official title

Systematic Use of DDAVP to Prevent Serum Sodium Overcorrection in Severe Hyponatremia: a Multicenter Open-label Randomized Controlled Trial

Overview

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

Detailed 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

Interventions

  • Drug DDAVP
    Posology: 4µg in 2ml IV solution Route of administration: Intravenous Duration of treatment: 48h maximum (additional doses every 6h)
  • Drug Standard hyponatremia treatment
    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

Primary outcome measures

  • reduced occurrence of overcorrection of serum sodium concentration (SNa) in the first 48 hours after randomization [Time frame: 48 hours after the randomization]
Secondary outcome measures (12)
  • the reversal of acute neurological symptoms in patients with neurological symptoms at inclusion [Time frame: 6 hours after the randomization]
  • ICU and hospital length of stay [Time frame: ICU or hospital discharge]
  • survival [Time frame: death after randomization]
  • the occurrence of central pontine myelinolysis diagnosed on clinical and MRI criteria [Time frame: 15 days after randomization]
  • the occurrence of any (pontine or extrapontine) osmotic demyelination as assessed by brain MRI [Time frame: 15 days after randomization]
  • on the percentage of patients with neurological symptoms at inclusion and reaching the initial goal of rapid partial pre-defined correction of SNa level [Time frame: 6 hours after the randomization]
  • the urine output between H0 and H6 [Time frame: 6 hours after the randomization]
  • the urine output between H6 and H12 [Time frame: 12 hours after the randomization]
  • the urine output between H12 and H24 [Time frame: 24 hours after the randomization]
  • the urine output between H24 and H48 [Time frame: 48 hours after the randomization]
  • the urine osmolality between H0 and H6 [Time frame: 6 hours after the randomization]
  • the urine osmolality between H6 and H12 [Time frame: 12 hours after the randomization]

Eligibility criteria

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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Open label
Primary purpose
Treatment

Study locations

France · 12 centers
  • Médecine Intensive et Réanimation - Centre Hospitalier Universitaire Amiens-Picardie — Amiens
  • Médecine Intensive et Réanimation - Hôpital Avicenne — Bobigny
  • Réanimation Polyvalente - Hôpital Jean Verdier — Bondy
  • Médecine Intensive et Réanimation - Hôpital Louis Mourier — Colombes
  • Réanimation Polyvalente et Surveillance continue - Centre Hospitalier Sud Francilien — Corbeil-Essonnes
  • Médecine Intensive et Réanimation - Hôpital Henri Mondor — Créteil
  • Médecine Intensive et Réanimation - Hôpital François Mitterand — Dijon
  • Réanimation Polyvalente - Centre Hospitalier Départemental Vendée — La Roche-sur-Yon
  • … and 4 more centers

Identifiers

NCT: NCT06020495 · APHP220676

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗