Efficacy and Safety of Rapid Intermittent Correction Compared With Slow Continuous Correction With Hypertonic Saline in Patient With Moderately Severe or Severe Symptomatic Severe Hyponatremia (SALSA Trial)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 178
- 试验地点
- 3
- 主要终点
- Incidence of overcorrection rate at any given period
研究概览
简要总结
This study will investigate efficacy and safety of rapid intermittent correction compared with slow continuous correction with hypertonic saline in patient with moderately severe or severe symptomatic severe hyponatremia
详细描述
Moderate to severe symptomatic hyponatremia requires prompt treatment with hypertonic saline. The extent and rate of increase in serum sodium (sNa) levels during treatment are critical. Several methods for continuous infusion of hypertonic saline were used to guide rate of fluid administered to achieve the required serum sodium target. As based on static model, they had a bias to over-correction of hyponatremia. Alternative approach to treatment with hypertonic fluid is to use small, fixed boluses to achieve controlled increments in sNa. However, there was no high quality evidence on whether hypertonic saline are best given in continuous infusion (preferred by most) or bolus injection. The aim of present study, a multi-center (Seoul National University Bundang Hospital [2016.8~], Seoul National University Boramae Medical Center [2016. 9~], Hallym University Dongtan Sacred Heart Hospital [2017.7~]), randomized, open labelled, controlled clinical trial, is to investigate efficacy and safety of rapid intermittent correction compared with slow continuous correction with hypertonic saline in patient with moderately severe or severe symptomatic severe hyponatremia. A total 178 patients, who suffer from symptomatic severe hyponatremia, will be enrolled and randomly assigned to receive either intermittent bolus infusion or slow continuous infusion by 3% hypertonic saline. Subjects will take different rate of 3% hypertonic saline for 24-48 hours stratified by severity of clinical symptoms. Serum sodium will be measured at every six hours during two days.
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
- •In emergency setting (2016.6-) and/or inpatients at ward (2018.9-)
- •Glucose corrected serum sodium ≤125 mmol/L
- •Patients with moderately severe or severe symptom
- •Moderately severe
- •:Nausea without vomiting Drowsy, Headache General weakness, myalgia
- •Severe :Vomiting, Stupor, Seizures, Coma (Glasgow Coma Scale ≤8)
- •written consent
排除标准
- •Pseudohyponatremia: serum osmolality > 275 mOsm/kg
- •If the serum osmolality is > 275 mOsm/kg but the BUN is ≥ 30 mg/dL, the patients can be registered if calculated serum osmolality (2 x plasma [Na] + [Glucose]/18) is <275 mOsm/kg
- •Primary polydipsia: urine osmolality ≤ 100 mOsm/kg
- •Glucose corrected serum sodium >125 mmol/L
- •Arterial hypotension (SBP <90mmHg and MAP <70mmHg)
- •Anuria or urinary outlet obstruction
- •Liver disease
- •transaminase levels >3 times the upper limit normal
- •Known LC with ascites or diuretics use or PSE Hx or Varix Hx
- •Uncontrolled diabetes mellitus (HbA1C > 9%)
- •Women who are pregnant or breast feeding
- •History of cardiac surgery excluding PCA, acute myocardial infarction, sustained ventricular tachycardia, ventricular fibrillation, acute coronary syndrome, cebrovascular trauma, and increased intracranial pressure within the 3 months prior to randomization
研究组 & 干预措施
Intermittent bolus group
<<Within 6hr>>
- Moderately Severe : 3% saline 2ml/kg over 20min *1 (unknown bwt 100ml)
- Severe :3% saline 2ml/kg over 20min *2 (unknown bwt 100ml)
<additional treatment> Repeat 3% saline 2ml/kg over 20min at every sample time point (at 1/6hr) till Na 5-9 mmol/L inc from initial Na and sx relief
<<During 6-24hr>>
- Moderately Severe or Severe
: Repeat 3% saline 2ml/kg over 20min at every sample time point(at 12/18/24hr) till Na 5-9 mmol/L inc from initial Na and sx relief
<<During 24-48hr>>
- Moderately Severe or Severe : Repeat 3% saline 2ml/kg over 20min at every sample time point (at 30/36/42/48hr) till Na 10-17 mmol/L inc from initial Na or Na ≥ 130mmol and sx relief
干预措施: 3% hypertonic saline (Drug)
slow continuous infusion group
<<Within 24hr>>
-
Moderately Severe: 3% saline 0.5ml/kg/hr (unknown bwt 25ml/hr)
-
Severe: 3% saline 1ml/kg/hr (unknown bwt 50ml/hr)
Infusion protocol modification as below by Na at every sample time point (at 1/6/12/18/24 hr)
If Na 5-9 mmol/L inc from initial Na and sx relief : stop 3% saline infusion regardless of △ Na
if △ Na inc <0.5mmol/hr or △ Na inc <3mmol/6hr : add 0.25ml/kg/hr, restart 0.5ml/kg/hr if previously stopped
if △ Na inc ≥0.5mmol/hr or △ Na inc ≥ 3mmol/6hr
: maintain infusion rate
<<During 24-48hr>>
- Moderately Severe and Severe
Infusion protocol modification as below by Na at every sample time point (at 30/36/42/48hr)
If Na 10-17 mmol/L inc from initial Na or Na ≥ 130mmol and sx relief
: stop 3% saline infusion regardless of △ Na
if △ Na inc <1.5mmol/6hr
: add 0.25ml/kg/hr or restart 0.25ml/kg/hr if previously stopped
if △ Na inc ≥ 1.5mmol/6hr
: maintain infusion rate
干预措施: 3% hypertonic saline (Drug)
结局指标
主要结局
Incidence of overcorrection rate at any given period
时间窗: up to 48 hours
Increase in sNa by \>12 mmol/L within 24 hours or Increase in sNa by \>18 mmol/L within 48 hours All subjects receive hypertonic saline by intermittent bolus or slow continuous infusion for 48 hours, serum Na will be measured.
次要结局
- Rapid improvement of symptoms(up to 24 hours)
- Time from treatment initiation to an increase of serum Na ≥ 5 mmol/L(up to 48 hours)
- Incidence of target correction rate(up to 48 hours)
- Time to serum Na >130 mmol/L(up to 48 hours)
- Length of hospital stay(up to 8 weeks)
- Incidence of additional treatment(up to 48 hours)
- Incidence of osmotic demyelinating syndrome confirmed by ICD -10 code or MRI(up to 48 hours)
- Incidence of relowering treatment(up to 48 hours)
- Change of Glasgow coma scale (GCS) ≤8(up to 48 hours)
研究者
Seon Ha Baek
Professor
Seoul National University Hospital