Efficacy and Safety of Rapid Intermittent Correction Compared With Slow Continuous Correction in Patients With Severe Hypernatremia (SALSA II Trial)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 178
- 试验地点
- 1
- 主要终点
- efficacy : Incidence of rapid change in sNa level within 24 hours defined as follows
研究概览
简要总结
This study will evaluate the efficacy and safety of rapid intermittent correction and slow correction with an electrolyte-free solution in patients with severe hypernatremia (glucose-corrected serum sodium, ≥ 155 mmol/L).
详细描述
Hypernatremia is defined as serum sodium (sNa) levels above 145 mmol/L and is caused by abnormalities in water balance, mainly in children, elderly, and critically ill patients. It occurs in 3% of hospitalized patients and in 9% of critically ill patients. Hypernatremia indicates hypertonic hyperosmolality and causes water outflow, resulting in cell dehydration. Most of the symptoms and signs of hypernatremia are due to brain abnormalities, which can progress to hyperventilation, muscle weakness, consciousness (lethargy), and coma. The short-term mortality rate of hypernatremia is 50%-60%. Decreased osmotic pressure in the extracellular fluid during correction of hyponatremia can cause cellular edema and permanent brain damage. The recommended sNa correction rate for acute hypernatremia is up to 1 mmol/L/h, whereas that for chronic hypernatremia is less than 0.5 mmol/L/h (approximately 10 mmol/L/day). However, these correction rates have only been studied and proven in pediatric patients. A recent study conducted on adults revealed that rapid correction (more than 0.5 mmol/L/h) was not associated with a higher risk for mortality, seizures, and alteration of consciousness. Several studies reported that excessively slow rates of sNa correction were associated with higher mortality, whereas rapid rates demonstrated lower mortality. There are no established guidelines for the Na correction rate for hypernatremia. The European and American guidelines recommend infusion of electrolyte-free water (10 mL/kg over 1 h or 3 mL/kg/h) for the management of overcorrection of hyponatremia. In the previously published SALSA I trial, 10 mL/kg over 1 h was applied as a method of re-lowering treatment in overly rapid correction of hyponatremia. However, this rapid intermittent bolus of electrolyte-free water has never been applied to treat hypernatremia.
The aim of this prospective, randomized, open-labeled, multi-center, and investigator-initiated trial is to determine whether a rapid and intermittent bolus of electrolyte-free water in hypernatremia can increase the incidence of rapid decrease in sNa level and increase the survival time compared to the slow continuous administration method. A total of 166 patients with severe hypernatremia will be enrolled and randomly assigned to receive either intermittent bolus or slow continuous infusion of 5% dextrose water. The participants will be divided into three groups according to age and sex and will receive 5% dextrose water for 2 days at different correction rates. Serum sodium will be measured every 3 h from the beginning to 6 h, followed by every 6 h until 48 h. In addition, urine sodium and potassium levels will be measured at baseline and 24 h. The PP (Per Protocol) analysis will be applied to enrolled participants who is infused with 75-125% of total planned volume of 5% dextrose water.
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
- •Patients who visit the emergency department and in-patients over 18 years
- •Severe hypernatremia: glucose-corrected serum sodium ≥ 155 mmol/L
- •Written consent
排除标准
- •Arterial hypotension requiring inotropes or vasopressors (systolic blood pressure < 90 mmHg and mean arterial pressure < 70 mmHg)
- •Anuria or bilateral urinary outlet obstruction
- •Uncontrolled diabetes mellitus (HbA1C > 9%) or glucose at baseline > 500 mg/dL or uncontrolled diabetic ketoacidosis or uncontrolled hyperosmolar hyperglycemic syndrome
- •Decompensated liver cirrhosis (LC) - Known LC with ascites or diuretic use or hepatic encephalopathy or varix
- •End-stage renal disease receiving renal replacement therapy
- •Uncontrolled Heart failure (regardless of LVEF)
- •Women who are pregnant or breast feeding
- •Patients with the following conditions within 30 days prior to randomization:
- •History of cardiac surgery excluding PCA, acute myocardial infarction, sustained ventricular tachycardia, ventricular fibrillation, acute coronary syndrome, and admission for heart failure
- •Uncontrolled increase of intracranial pressure
- •The subjects judged by investigators to have difficulty continuing the trial were also excluded.
- •The case the subjects does not consent to the study
研究组 & 干预措施
Rapid intermittent bolus group
A : males < 65 ; B : females < 65 or males ≥ 65 ; C : females ≥ 65 yrs
<During the first 3 h>
Primary treatment over 1h A: 5DW 8 B: 5DW 7 C: 5DW 6 mL/kg
If undercorrected, Repeat the 5DW amount infused during primary treatment after 3 h
<At 3-24 h> Modify protocol based on sNa at each time point (6/12/18/24 h)
Check U/S ratio at 0 h
- undercorrection < 0.5: repeat the amount infused during primary treatment q 3 h
≥ 0.5: repeat the amount infused during primary treatment q 6 h
- target correction < 0.5: repeat the amount infused during primary treatment q 6 h ≥ 0.5: stop the infusion
<At 24-48 h> Modify protocol based on sNa at each time point (30/36/42/48 h)
Check U/S ratio at 24 h
- undercorrection < 0.5: repeat the amount infused during primary treatment q 3 h
≥ 0.5: repeat the amount infused during primary treatment q 6 h
- target correction < 0.5: repeat the amount infused during primary treatment q 6 h ≥ 0.5: stop the infusion
干预措施: Dextrose 5% in water (Drug)
Slow continuous infusion group
Participants will be divided into three groups same as above
<During the first 3 h>
Primary treatment A: 5DW 1.8 B: 5DW 1.57 C: 5DW 1.35 mL/kg/h
Modify protocol as described below based on sNa measurement at 3 h
- undercorrection: maintain the infusion rate
- target correction: stop the infusion
<At 3-24 h> Modify protocol based on sNa measurement at each time point (6/12/18/24 h)
Check U/S ratio at 0 h
• undercorrection
< 0.5: increase the infusion rate to twice that of the primary treatment
≥ 0.5: maintain the infusion rate
• target correction
< 0.5: maintain the infusion rate
≥ 0.5: stop the infusion
<At 24-48 h> Modify protocol based on sNa measurement at each time point (30/36/42/48 h)
Check U/S ratio at 24 h
• undercorrection
< 0.5: increase the infusion rate to twice that of the primary treatment
≥ 0.5: maintain the infusion rate
• target correction
< 0.5: maintain the infusion rate
≥ 0.5: stop the infusion
干预措施: Dextrose 5% in water (Drug)
结局指标
主要结局
efficacy : Incidence of rapid change in sNa level within 24 hours defined as follows
时间窗: up to 24 hours
Change in sNa by ≥ 6 mmol/L or Na ≤ 150 mmol/L within 24 hours All subjects will receive 5% dextrose water by rapid intermittent bolus or slow continuous infusion for 48 h, and sNa levels will be measured.
次要结局
- difference in sNa levels 6 hours after the initial test(up to 6 hours)
- the 28-day survival rate(up to 28 days)
- Incidence of rapid change in sNa level within 48 hours defined as follows(up to 48 hours)
- volume of 5% dextrose water infused during 48 hours(up to 48 hours)