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

NCT04949139 | Completed Phase 4 DMC

• 1 other identifier: B-2104-680-003
• Study Type: interventional
• Target: 178
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the efficacy and safety of rapid intermittent correction and slow correction with an electrolyte-free solution in patients with severe hypernatremia (glucose-corrected serum sodium, ≥ 155 mmol/L).

Conditions

Hypernatremia

Keywords

Hypernatremia; Treatment; 5% dextrose water

Outcome Measures

Primary Outcomes (1)

• efficacy : Incidence of rapid change in sNa level within 24 hours defined as follows

  Change in sNa by ≥ 6 mmol/L or Na ≤ 150 mmol/L within 24 hours All subjects will receive 5% dextrose water by rapid intermittent bolus or slow continuous infusion for 48 h, and sNa levels will be measured.

  up to 24 hours

Secondary Outcomes (4)

• the 28-day survival rate

  up to 28 days

• difference in sNa levels 6 hours after the initial test

  up to 6 hours

• volume of 5% dextrose water infused during 48 hours

  up to 48 hours

• Incidence of rapid change in sNa level within 48 hours defined as follows

  up to 48 hours

Other Outcomes (10)

• Target correction rate

  up to 48 hours

• Incidence of undercorrection:

  up to 48 hours

• Length of hospital stay

  up to 8 weeks

Study Arms (2)

Rapid intermittent bolus group

ACTIVE COMPARATOR

A : males \< 65 ; B : females \< 65 or males ≥ 65 ; C : females ≥ 65 yrs \<During the first 3 h\> Primary treatment over 1h A: 5DW 8 B: 5DW 7 C: 5DW 6 mL/kg If undercorrected, Repeat the 5DW amount infused during primary treatment after 3 h \<At 3-24 h\> Modify protocol based on sNa at each time point (6/12/18/24 h) Check U/S ratio at 0 h * undercorrection \< 0.5: repeat the amount infused during primary treatment q 3 h ≥ 0.5: repeat the amount infused during primary treatment q 6 h * target correction \< 0.5: repeat the amount infused during primary treatment q 6 h ≥ 0.5: stop the infusion \<At 24-48 h\> Modify protocol based on sNa at each time point (30/36/42/48 h) Check U/S ratio at 24 h * undercorrection \< 0.5: repeat the amount infused during primary treatment q 3 h ≥ 0.5: repeat the amount infused during primary treatment q 6 h * target correction \< 0.5: repeat the amount infused during primary treatment q 6 h ≥ 0.5: stop the infusion

Drug: Dextrose 5% in water

Slow continuous infusion group

ACTIVE COMPARATOR

Participants will be divided into three groups same as above \<During the first 3 h\> Primary treatment A: 5DW 1.8 B: 5DW 1.57 C: 5DW 1.35 mL/kg/h Modify protocol as described below based on sNa measurement at 3 h * undercorrection: maintain the infusion rate * target correction: stop the infusion \<At 3-24 h\> Modify protocol based on sNa measurement at each time point (6/12/18/24 h) Check U/S ratio at 0 h • undercorrection \< 0.5: increase the infusion rate to twice that of the primary treatment ≥ 0.5: maintain the infusion rate • target correction \< 0.5: maintain the infusion rate ≥ 0.5: stop the infusion \<At 24-48 h\> Modify protocol based on sNa measurement at each time point (30/36/42/48 h) Check U/S ratio at 24 h • undercorrection \< 0.5: increase the infusion rate to twice that of the primary treatment ≥ 0.5: maintain the infusion rate • target correction \< 0.5: maintain the infusion rate ≥ 0.5: stop the infusion

Drug: Dextrose 5% in water

Interventions

Dextrose 5% in water DRUG

Reducing the sodium concentration

Rapid 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:

• Patients who visit the emergency department and in-patients over 18 years
• Severe hypernatremia: glucose-corrected serum sodium ≥ 155 mmol/L
• Written consent

You may not qualify if:

• Arterial hypotension requiring inotropes or vasopressors (systolic blood pressure \< 90 mmHg and mean arterial pressure \< 70 mmHg)
• Anuria or bilateral urinary outlet obstruction
• Uncontrolled diabetes mellitus (HbA1C \> 9%) or glucose at baseline \> 500 mg/dL or uncontrolled diabetic ketoacidosis or uncontrolled hyperosmolar hyperglycemic syndrome
• Decompensated liver cirrhosis (LC) - Known LC with ascites or diuretic use or hepatic encephalopathy or varix
• End-stage renal disease receiving renal replacement therapy
• Uncontrolled Heart failure (regardless of LVEF)
• Women who are pregnant or breast feeding
• Patients with the following conditions within 30 days prior to randomization:
• History of cardiac surgery excluding PCA, acute myocardial infarction, sustained ventricular tachycardia, ventricular fibrillation, acute coronary syndrome, and admission for heart failure
• Uncontrolled increase of intracranial pressure
• The subjects judged by investigators to have difficulty continuing the trial were also excluded.
• The case the subjects does not consent to the study

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Hallym University Dongtan Sacred Heart Hospital

Hwaseong-si, Gyeonggi-do, 18450, South Korea

Location

Related Publications (11)

• Qian Q. Hypernatremia. Clin J Am Soc Nephrol. 2019 Mar 7;14(3):432-434. doi: 10.2215/CJN.12141018. Epub 2019 Feb 6. No abstract available.

  PMID: 30728169 BACKGROUND

• Chauhan K, Pattharanitima P, Patel N, Duffy A, Saha A, Chaudhary K, Debnath N, Van Vleck T, Chan L, Nadkarni GN, Coca SG. Rate of Correction of Hypernatremia and Health Outcomes in Critically Ill Patients. Clin J Am Soc Nephrol. 2019 May 7;14(5):656-663. doi: 10.2215/CJN.10640918. Epub 2019 Apr 4.

  PMID: 30948456 BACKGROUND

• Hillier TA, Abbott RD, Barrett EJ. Hyponatremia: evaluating the correction factor for hyperglycemia. Am J Med. 1999 Apr;106(4):399-403. doi: 10.1016/s0002-9343(99)00055-8.

  PMID: 10225241 BACKGROUND

• Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med. 2000 May 18;342(20):1493-9. doi: 10.1056/NEJM200005183422006. No abstract available.

  PMID: 10816188 BACKGROUND

• Sterns RH. Evidence for Managing Hypernatremia: Is It Just Hyponatremia in Reverse? Clin J Am Soc Nephrol. 2019 May 7;14(5):645-647. doi: 10.2215/CJN.02950319. Epub 2019 Apr 4. No abstract available.

  PMID: 31064771 BACKGROUND

• Cabassi A, Tedeschi S. Severity of community acquired hypernatremia is an independent predictor of mortality: a matter of water balance and rate of correction. Intern Emerg Med. 2017 Oct;12(7):909-911. doi: 10.1007/s11739-017-1693-x. Epub 2017 Jul 1. No abstract available.

  PMID: 28669048 BACKGROUND

• Lindner G, Funk GC. Hypernatremia in critically ill patients. J Crit Care. 2013 Apr;28(2):216.e11-20. doi: 10.1016/j.jcrc.2012.05.001. Epub 2012 Jul 2.

  PMID: 22762930 BACKGROUND

• Bataille S, Baralla C, Torro D, Buffat C, Berland Y, Alazia M, Loundou A, Michelet P, Vacher-Coponat H. Undercorrection of hypernatremia is frequent and associated with mortality. BMC Nephrol. 2014 Feb 21;15:37. doi: 10.1186/1471-2369-15-37.

  PMID: 24559470 BACKGROUND

• Alshayeb HM, Showkat A, Babar F, Mangold T, Wall BM. Severe hypernatremia correction rate and mortality in hospitalized patients. Am J Med Sci. 2011 May;341(5):356-60. doi: 10.1097/MAJ.0b013e31820a3a90.

  PMID: 21358313 BACKGROUND

• Sterns RH, Silver SM. Salt and water: read the package insert. QJM. 2003 Aug;96(8):549-52. doi: 10.1093/qjmed/hcg102. No abstract available.

  PMID: 12897339 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Hypernatremia

Interventions

Glucose; Water

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds

Study Officials

• Sejoong Kim, PhD

  Seoul National University Bundang Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2021
• First Posted: July 2, 2021
• Study Start: May 1, 2021
• Primary Completion: January 23, 2025
• Study Completion: February 22, 2025
• Last Updated: August 29, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)