Efficacy and Safety of Rapid Intermittent Compared With Slow Continuous Correction in Severe Hyponatremia Patients

Hyponatremia Symptomatic Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02887469
• Other study ID #: B1605346003
• Status: Completed
• Phase: Phase 4
• Start date: August 2016
• Est. completion date: September 30, 2019

Study information

• Verified date: April 2020
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 178
• Est. completion date: September 30, 2019
• Est. primary completion date: September 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Hyponatremia
• Hyponatremia Symptomatic

Intervention

Drug:
• 3% hypertonic saline
The same as above

Locations

Country	Name	City	State
Korea, Republic of	Hallym University Dongtan Sacred Hospital	Hwaseong-si	Gyeonggi-do
Korea, Republic of	Seoul National University Bundang Hospital Clinical Trial Center	Seongnam	Gyeonggi-do
Korea, Republic of	Seoul National University Boramae Hospital	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Hospital	National Research Foundation of Korea

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (1)

Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, Decaux G, Fenske W, Hoorn EJ, Ichai C, Joannidis M, Soupart A, Zietse R, Haller M, van der Veer S, Van Biesen W, Nagler E; Hyponatraemia Guideline Development Group. Clinical practice guidel — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of overcorrection rate at any given period	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.	up to 48 hours
Secondary	Rapid improvement of symptoms	Change of symptoms from baseline to 24 hours after hypertonic fluid treatment	up to 24 hours
Secondary	Time from treatment initiation to an increase of serum Na = 5 mmol/L		up to 48 hours
Secondary	Incidence of target correction rate	Target correction rate is defined by achieved serum Na <10 mmol/L within 24 hours, achieved serum Na <18 mmol/L within 48 hours	up to 48 hours
Secondary	Time to serum Na >130 mmol/L	Time from treatment initiation to achieved serum Na> 130mmol/L	up to 48 hours
Secondary	Length of hospital stay		up to 8 weeks
Secondary	Incidence of additional treatment	Additional treatment is performed if symptom is not relieved or undercorrection develops (achieved Na < 5mmol/L with 24 hours or achieved Na <12mmol/L within 48 hours)	up to 48 hours
Secondary	Incidence of osmotic demyelinating syndrome confirmed by ICD -10 code or MRI		up to 48 hours
Secondary	Incidence of relowering treatment	Relowering treatment is performed as below if achieved serum Na is <10 mmol/L within 24 hours, achieved serum Na is <18 mmol/L within 48 hours.; discontinuing ongoing active treatment; start infusion of 10ml/kg of 5% dextrose over 1hr ± desmopressin 2mcg IV	up to 48 hours
Secondary	Change of Glasgow coma scale (GCS) =8	Change in GCS of hyponatremia symptoms at pretreatment, 24 hours, and 48 hours after treatment	up to 48 hours