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

Phase 3RecruitingNCT06020495

Assistance Publique - Hôpitaux de Paris260 enrolled

Overview

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

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

260

Conditions

Hyponatremia

Interventions

DDAVPDRUG

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

Standard hyponatremia treatmentDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

Locations (12)

Médecine Intensive et Réanimation - Centre Hospitalier Universitaire Amiens-Picardie

Amiens, France

RECRUITING

Médecine Intensive et Réanimation - Hôpital Avicenne

Bobigny, France

Outcomes

Primary Outcomes

reduced occurrence of overcorrection of serum sodium concentration (SNa) in the first 48 hours after randomization

proportion of patients with SNa level overcorrection : any risk factor: SNa increase \> 6 mmol/L in less than H24, or \>12 mmol/L in less than H48. Without risk factor: SNa increase \> 10 mmol/L in less than H24, or \> 18 mmol/L in less than H48

Time frame: 48 hours after the randomization

Secondary Outcomes

the reversal of acute neurological symptoms in patients with neurological symptoms at inclusion

proportion of patients with neurological symptoms at inclusion and who subsequently have a normal Glasgow Coma Scale at H6

Time frame: 6 hours after the randomization

ICU and hospital length of stay

length of ICU and hospital stay

Time frame: ICU or hospital discharge

survival

time to death after inclusion

Time frame: death after randomization

the occurrence of central pontine myelinolysis diagnosed on clinical and MRI criteria

proportion of patients with the occurrence of central pontine myelinolysis diagnosed on clinical and MRI criteria at day 15 (or earlier if clinically justified)

Time frame: 15 days after randomization

the occurrence of any (pontine or extrapontine) osmotic demyelination as assessed by brain MRI

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)

Time frame: 15 days after randomization

Central Contacts

GAUDRY Stéphane

CONTACT

01.48.95.55.55 stephane.gaudry@aphp.fr

DECHANET Aline

CONTACT

01 40 25 78 30 aline.dechanet@aphp.fr

Data from ClinicalTrials.gov

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