Systematic Use of DDAVP to Prevent Serum Sodium Overcorrection in Severe Hyponatremia: a Multicenter Open-label Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 260
- 试验地点
- 12
- 主要终点
- reduced occurrence of overcorrection of serum sodium concentration (SNa) in the first 48 hours after randomization
研究概览
简要总结
ICU patients with severe hyponatremia and a high risk of rapid SNa overcorrection.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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)
研究组 & 干预措施
DDAVP
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
干预措施: DDAVP (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
干预措施: Standard hyponatremia treatment (Drug)
结局指标
主要结局
reduced occurrence of overcorrection of serum sodium concentration (SNa) in the first 48 hours after randomization
时间窗: 48 hours after the 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
次要结局
- survival(death after randomization)
- the urine output between H24 and H48(48 hours after the randomization)
- the urine osmolality between H24 and H48(48 hours after the randomization)
- amount of hypotonic fluids administration(48 hours after the randomization)
- the reversal of acute neurological symptoms in patients with neurological symptoms at inclusion(6 hours after the randomization)
- the occurrence of central pontine myelinolysis diagnosed on clinical and MRI criteria(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(6 hours after the randomization)
- the urine output between H6 and H12(12 hours after the randomization)
- SNa level correction rate between H0 and H48(48 hours after the randomization)
- the occurrence of any new neurological sign in relation with hyponatremia in patients with a normal neurological exam at inclusion or on the reappearance of any neurological sign in relation with hyponatremia after inclusion(28 days after randomization)
- the occurrence of any (pontine or extrapontine) osmotic demyelination as assessed by brain MRI(15 days after randomization)
- SNa level correction rate between H0 and H24(24 hours after the randomization)
- amount of sodium and potassium administered between H0 and H24(24 hours after the randomization)
- ICU and hospital length of stay(ICU or hospital discharge)
- the urine osmolality between H6 and H12(12 hours after the randomization)
- the urine osmolality between H12 and H24(24 hours after the randomization)
- the urine output between H0 and H6(6 hours after the randomization)
- the urine output between H12 and H24(24 hours after the randomization)
- the urine osmolality between H0 and H6(6 hours after the randomization)
- the maximal change of SNa level between H0 and H24(24 hours after the randomization)
- the maximal change of SNa level between H0 and H48(48 hours after the randomization)
- amount of sodium and potassium administered between H0 and H48(48 hours after the randomization)
- the occurrence of excessive re-lowering of sodium(48 hours after the randomization)