Clinical trial NCT02887469: Efficacy and Safety of Rapid Intermittent Compared With Slow Continuous Correction in Severe Hyponatremia Patients
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hyponatremia Symptomatic
Keywords: Hyponatremia
Hypertonic saline
Treatment
Osmotic demyelination syndrome
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: National Research Foundation of Korea
First posted: 2016-09-02
Enrollment: 178
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 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of overcorrection rate at any given period
timeFrame: up to 48 hours
Secondary outcomes:
measure: Rapid improvement of symptoms
timeFrame: up to 24 hours
measure: Time from treatment initiation to an increase of serum Na ≥ 5 mmol/L
timeFrame: up to 48 hours
measure: Incidence of target correction rate
timeFrame: up to 48 hours
measure: Time to serum Na >130 mmol/L
timeFrame: up to 48 hours
measure: Length of hospital stay
timeFrame: up to 8 weeks
measure: Incidence of additional treatment
timeFrame: up to 48 hours
measure: Incidence of osmotic demyelinating syndrome confirmed by ICD -10 code or MRI
timeFrame: up to 48 hours
measure: Incidence of relowering treatment
timeFrame: up to 48 hours
measure: Change of Glasgow coma scale (GCS) ≤8
timeFrame: up to 48 hours
Other outcomes:
Locations:
city: Hwaseong-si
country: Korea, Republic of
facility: Hallym University Dongtan Sacred Hospital
state: Gyeonggi-do
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital Clinical Trial Center
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Boramae Hospital
Study officials:
affiliation: Hallym University Dongtan Sacred Hospital
name: Seon Ha Baek, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.