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

Sponsor
Seoul National University Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT02887469
Collaborator
National Research Foundation of Korea (Other)
178
3
2
37.9
59.3
1.6

Study Details

Study Description

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
  • 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 Design

Study Type:
Interventional
Actual 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 :
Aug 1, 2016
Actual Primary Completion Date :
Sep 30, 2019
Actual Study Completion Date :
Sep 30, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Incidence of overcorrection rate at any given period [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 [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 [up to 48 hours]

  3. Incidence of target correction rate [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 [up to 48 hours]

    Time from treatment initiation to achieved serum Na> 130mmol/L

  5. Length of hospital stay [up to 8 weeks]

  6. Incidence of additional treatment [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 [up to 48 hours]

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

  9. Change of Glasgow coma scale (GCS) ≤8 [up to 48 hours]

    Change in GCS of hyponatremia symptoms at pretreatment, 24 hours, and 48 hours after treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Hallym University Dongtan Sacred Hospital Hwaseong-si Gyeonggi-do Korea, Republic of 445-907
2 Seoul National University Bundang Hospital Clinical Trial Center Seongnam Gyeonggi-do Korea, Republic of 13605
3 Seoul National University Boramae Hospital Seoul Korea, Republic of

Sponsors and Collaborators

  • Seoul National University Hospital
  • National Research Foundation of Korea

Investigators

  • Principal Investigator: Seon Ha Baek, PhD, Hallym University Dongtan Sacred Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Seon Ha Baek, Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT02887469
Other Study ID Numbers:
  • B1605346003
First Posted:
Sep 2, 2016
Last Update Posted:
Apr 9, 2020
Last Verified:
Apr 1, 2020
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by Seon Ha Baek, Professor, Seoul National University Hospital
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 9, 2020