ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02887469
Recruitment Status : Recruiting
First Posted : September 2, 2016
Last Update Posted : July 13, 2017
Sponsor:
Collaborator:
National Research Foundation of Korea
Information provided by (Responsible Party):
Seon Ha Baek, Seoul National University Hospital

Brief 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

Condition or disease Intervention/treatment Phase
Hyponatremia Symptomatic Drug: 3% hypertonic saline Phase 4

Detailed 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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 178 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Study Start Date : August 2016
Estimated Primary Completion Date : July 2018
Estimated Study Completion Date : July 2018

Arm Intervention/treatment
Active Comparator: 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
Drug: 3% hypertonic saline
The same as above

Active Comparator: 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

Drug: 3% hypertonic saline
The same as above




Primary Outcome Measures :
  1. Incidence of overcorrection rate at any given period [ Time Frame: 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.


Secondary Outcome Measures :
  1. Rapid improvement of symptoms [ Time Frame: up to 24 hours ]
    Change of symptoms from baseline to 24 hours after hypertonic fluid treatment

  2. Time from treatment initiation to an increase of serum Na ≥ 5 mmol/L [ Time Frame: up to 48 hours ]
  3. Incidence of target correction rate [ Time Frame: up to 48 hours ]
    Target correction rate is defined by achieved serum Na <10 mmol/L within 24 hours, achieved serum Na <18 mmol/L within 48 hours

  4. Time to serum Na >130 mmol/L [ Time Frame: up to 48 hours ]
    Time from treatment initiation to achieved serum Na> 130mmol/L

  5. Length of hospital stay [ Time Frame: up to 8 weeks ]
  6. Incidence of additional treatment [ Time Frame: up to 48 hours ]
    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)

  7. Incidence of osmotic demyelinating syndrome confirmed by ICD -10 code or MRI [ Time Frame: up to 48 hours ]
  8. Incidence of relowering treatment [ Time Frame: up to 48 hours ]

    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.

    1. discontinuing ongoing active treatment
    2. start infusion of 10ml/kg of 5% dextrose over 1hr ± desmopressin 2mcg IV

  9. Change of Glasgow coma scale (GCS) ≤8 [ Time Frame: up to 48 hours ]
    Change in GCS of hyponatremia symptoms at pretreatment, 24 hours, and 48 hours after treatment



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • In emergency setting
  • 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
  • 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

    • bilirubin > 2 mg/dl, transaminase levels >2.5 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02887469


Contacts
Contact: Seon Ha Baek, MD 82 31 787 7088 haya2001@snubh.org

Locations
Korea, Republic of
Seoul National University Bundang Hospital Clinical Trial Center Recruiting
Seongnam, Gyeonggi-do, Korea, Republic of, 13605
Contact: Hyunjin Cho    82 31 787 7030    10871@snubh.org   
Sponsors and Collaborators
Seoul National University Hospital
National Research Foundation of Korea
Investigators
Principal Investigator: Seon Ha Baek, MD Seoul National University Bundang Hospital

Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Seon Ha Baek, Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT02887469     History of Changes
Other Study ID Numbers: B1605346003
First Posted: September 2, 2016    Key Record Dates
Last Update Posted: July 13, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Seon Ha Baek, Seoul National University Hospital:
Hyponatremia
Hypertonic saline
Treatment
Osmotic demyelination syndrome

Additional relevant MeSH terms:
Hyponatremia
Water-Electrolyte Imbalance
Metabolic Diseases