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

NCT02887469 | Completed Phase 4 DMC

• 1 other identifier: B1605346003
• Study Type: interventional
• Target: 178
• Locations: 1 country
• Sites: 3

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

Conditions

Hyponatremia Symptomatic

Keywords

Hyponatremia; Hypertonic saline; Treatment; Osmotic demyelination syndrome

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Rapid improvement of symptoms

  up to 24 hours

• Time from treatment initiation to an increase of serum Na ≥ 5 mmol/L

  up to 48 hours

• Incidence of target correction rate

  up to 48 hours

• Time to serum Na >130 mmol/L

  up to 48 hours

• Length of hospital stay

  up to 8 weeks

Study Arms (2)

Intermittent bolus group

ACTIVE COMPARATOR

\<\<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

slow continuous infusion group

ACTIVE COMPARATOR

\<\<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

Interventions

3% hypertonic saline DRUG

The same as above

Intermittent bolus group; slow continuous infusion group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seoul National University Hospital: lead
• National Research Foundation of Korea: collaborator

Study Sites (3)

Hallym University Dongtan Sacred Hospital

Hwaseong-si, Gyeonggi-do, 445-907, South Korea

Location

Seoul National University Bundang Hospital Clinical Trial Center

Seongnam-si, Gyeonggi-do, 13605, South Korea

Location

Seoul National University Boramae Hospital

Seoul, South Korea

Location

Related Publications (3)

• 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 guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol. 2014 Feb 25;170(3):G1-47. doi: 10.1530/EJE-13-1020. Print 2014 Mar.

  PMID: 24569125 RESULT

• Baek SH, Jo YH, Ahn S, Medina-Liabres K, Oh YK, Lee JB, Kim S. Risk of Overcorrection in Rapid Intermittent Bolus vs Slow Continuous Infusion Therapies of Hypertonic Saline for Patients With Symptomatic Hyponatremia: The SALSA Randomized Clinical Trial. JAMA Intern Med. 2021 Jan 1;181(1):81-92. doi: 10.1001/jamainternmed.2020.5519.

  PMID: 33104189 DERIVED

• Lee A, Jo YH, Kim K, Ahn S, Oh YK, Lee H, Shin J, Chin HJ, Na KY, Lee JB, Baek SH, Kim S. Efficacy and safety of rapid intermittent correction compared with slow continuous correction with hypertonic saline in patients with moderately severe or severe symptomatic hyponatremia: study protocol for a randomized controlled trial (SALSA trial). Trials. 2017 Mar 29;18(1):147. doi: 10.1186/s13063-017-1865-z.

  PMID: 28356136 DERIVED

MeSH Terms

Conditions

Hyponatremia

Interventions

Saline Solution, Hypertonic

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Hypertonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Seon Ha Baek, PhD

  Hallym University Dongtan Sacred Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 1, 2016
• First Posted: September 2, 2016
• Study Start: August 1, 2016
• Primary Completion: September 30, 2019
• Study Completion: September 30, 2019
• Last Updated: April 9, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (3)