Clinical trial NCT04949139: Efficacy and Safety of Rapid Intermittent Correction Compared With Slow Continuous Correction in Patients With Severe Hypernatremia
Official title: Efficacy and Safety of Rapid Intermittent Correction Compared With Slow Continuous Correction in Patients With Severe Hypernatremia (SALSA II Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Hypernatremia
Keywords: Hypernatremia
Treatment
5% dextrose water
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
First posted: 2021-07-02
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Patients who visit the emergency department and in-patients over 18 years
* Severe hypernatremia: glucose-corrected serum sodium ≥ 155 mmol/L
* Written consent

Exclusion Criteria:

* 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:

  1. History of cardiac surgery excluding PCA, acute myocardial infarction, sustained ventricular tachycardia, ventricular fibrillation, acute coronary syndrome, and admission for heart failure
  2. 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

Primary outcomes:
measure: efficacy : Incidence of rapid change in sNa level within 24 hours defined as follows
timeFrame: up to 24 hours
Secondary outcomes:
measure: the 28-day survival rate
timeFrame: up to 28 days
measure: difference in sNa levels 6 hours after the initial test
timeFrame: up to 6 hours
measure: volume of 5% dextrose water infused during 48 hours
timeFrame: up to 48 hours
measure: Incidence of rapid change in sNa level within 48 hours defined as follows
timeFrame: up to 48 hours
Other outcomes:
measure: Target correction rate
timeFrame: up to 48 hours
measure: Incidence of undercorrection:
timeFrame: up to 48 hours
measure: Length of hospital stay
timeFrame: up to 8 weeks
measure: Number of uses of desmopressin
timeFrame: up to 48 hours
measure: Incidence of overcorrection
timeFrame: up to 48 hours
measure: Incidence of cerebral edema documented via brain CT at 48 hours in patients with overcorrection
timeFrame: up to 48 hours
measure: Incidence of osmotic demyelinating syndrome confirmed by ICD-10 code or MRI
timeFrame: up to 48 hours
measure: Glasgow coma scale at pretreatment, 6 hours, 24 hours, and 48 hours
timeFrame: up to 48 hours
measure: In-hospital mortality
timeFrame: up to 28 days
measure: Incidence of administrated intravenous volume of ≥ 3 L/day, except for fluids administrated according to the protocol
timeFrame: up to 48 hours
Locations:
city: Hwaseong
country: Korea, Republic of
facility: Hallym University Dongtan Sacred Heart Hospital
state: Gyeonggi-do
Study officials:
affiliation: Seoul National University Bundang Hospital
name: Sejoong Kim, PhD
role: STUDY_DIRECTOR
References:
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