Lower vs. Standard Insulin-Dextrose Doses for Treating Mild to Moderate Hyperkalemia in the Emergency Department

NCT06724991 | Enrolling By Invitation

• 2 other identifiers: 2024101-14273RSCH ID-24-06414-1Q3
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial aims to evaluate the safety and efficacy of a lower dose insulin compared to the conventional dose for treating mild to moderate hyperkalemia, a condition characterized by elevated serum potassium levels below 6.4 mmol/L. The study focuses on adult patients in the emergency department. The primary objective is to determine whether the efficacy of lower doses of insulin and dextrose is non-inferior to conventional doses in reducing serum potassium levels in patients with mild to moderate hyperkalemia. The research compares two regimens: 5 units of insulin with 25 mL of dextrose 50% versus 10 units of insulin with 50 mL of dextrose 50%, assessing the mean reduction in serum potassium levels, the incidence of hypoglycemia, and the risk of extravasation injury. Participants will be monitored in the emergency department for 6 hours. Serum potassium levels will be measured at 1, 2, 4, and 6 hours post-intervention, while blood glucose levels will be monitored at 30, 60, 90, 120, 240, 300, and 360 minutes post-intervention.

Conditions

Hyperkalemia

Keywords

hyperkalemia; hypoglycemia; lower dose insulin; extravasation injury

Outcome Measures

Primary Outcomes (1)

• Mean potassium difference between baseline and 1 hour post therapy

  The difference in serum potassium level between baseline and one hour post therapy will be compared between the two arms

  From administration of actrapid to the first hour after administration of actrapid

Secondary Outcomes (3)

• Incidence of hypoglycaemia within 6 hours of insulin administration

  From administration of actrapid until the 6 hours after administration of actrapid

• Number of patients requiring rescue treatment for persistent hyperkalaemia (> 5.7 mmol/L) despite initial treatment

  From administration of actrapid until the 6 hours after administration of actrapid

• Mortality in patients within 7 days

  From enrolment to 7 days after receiving interventional treatment

Study Arms (2)

Conventional Dose Therapy

ACTIVE COMPARATOR

Traditional treatment involves a higher insulin dose with dextrose to mitigate hypoglycemia risk while effectively lowering potassium. Ingredients: Actrapid insulin, Dextrose 50% Dosage: 10 units of Actrapid insulin with 50 cc of Dextrose 50% Route of Administration: Intravenous (IV) Frequency: Administered as a single dose at the start of treatment Procedure: The conventional dose has been the standard of care but carries a significant risk of hypoglycemia.

Procedure: Conventional Dose Therapy

Lower Dose Therapy

EXPERIMENTAL

Standard treatment of hyperkalemia includes insulin to shift potassium intracellularly and dextrose to mitigate the risk of hypoglycemia. This arm will be active intervention which means to compare with traditional dose of insulin and investigate if lower dose of insulin is non inferior in reducing serum potassium level in patient with mild and moderate hyperkalemia. Ingredients: Actrapid insulin, Dextrose 50% Dosage: 5 units of Actrapid insulin with 25 cc of Dextrose 50% Route of Administration: Intravenous (IV) Frequency: Administered as a single dose at the start of treatment Procedure: Lower-dose insulin is administered with dextrose to potentially reduce hypoglycemic risk while achieving effective potassium reduction.

Procedure: Lower Dose Therapy

Interventions

Lower Dose Therapy PROCEDURE

The group receiving the lower-dose therapy consists of 5 units of Actrapid (insulin) with 25cc of Dextrose 50%. This intervention is the focus of the clinical trial and is being investigated to determine if it achieves a comparable reduction in potassium levels with fewer potential complications. The aim is to establish it as a non-inferior alternative to conventional-dose therapy in the management of mild and moderate hyperkalemia.

Lower Dose Therapy

Conventional Dose Therapy PROCEDURE

The group receiving the conventional-dose therapy, consisting of 10 units of Actrapid (insulin) with 50cc of Dextrose 50%, which is currently in use as a standard practice in emergency departments for managing mild and moderate hyperkalemia. This dosing regimen aligns with established clinical guidelines and is widely accepted as an effective approach in controlling potassium levels.

Conventional Dose Therapy

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patient \>18 years old in emergency department (ED) with serum potassium 5.7 mmol/L to 6.4 mmol/L for non-haemolysed serum sample

You may not qualify if:

• Adolescent/ paediatric age group
• Patients who are in diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS)
• Pre-treatment blood glucose less than 4 mmol/L
• Requiring intraveneous (IV) infusion of insulin, nebulised salbutamol and IV sodium bicarbonate during screening
• Patient requiring resuscitation (ie: hemodynamically unstable) or requiring high flow oxygen (face mask \> 5L/min) or Modified Early Warning Score \> 4 during recruitment.

Sponsors & Collaborators

• University of Malaya: lead

Study Sites (1)

University Malaya Medical Centre

Kuala Lumpur, Malaysia

Location

Related Publications (12)

• Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024 Apr;105(4S):S117-S314. doi: 10.1016/j.kint.2023.10.018. No abstract available.

  PMID: 38490803 BACKGROUND

• Verdier M, DeMott JM, Peksa GD. A comparison of insulin doses for treatment of hyperkalaemia in intensive care unit patients with renal insufficiency. Aust Crit Care. 2022 May;35(3):258-263. doi: 10.1016/j.aucc.2021.05.004. Epub 2021 Jun 21.

  PMID: 34167889 BACKGROUND

• Schafers S, Naunheim R, Vijayan A, Tobin G. Incidence of hypoglycemia following insulin-based acute stabilization of hyperkalemia treatment. J Hosp Med. 2012 Mar;7(3):239-42. doi: 10.1002/jhm.977.

  PMID: 22489323 BACKGROUND

• Pierce DA, Russell G, Pirkle JL Jr. Incidence of Hypoglycemia in Patients With Low eGFR Treated With Insulin and Dextrose for Hyperkalemia. Ann Pharmacother. 2015 Dec;49(12):1322-6. doi: 10.1177/1060028015607559. Epub 2015 Sep 28.

  PMID: 26416951 BACKGROUND

• Pearson SC, O'Connor K, Keller K, Hodge TJ, Nesbit R. Efficacy of standard- vs reduced-dose insulin for treatment of hyperkalemia: A quasi-experiment. Am J Health Syst Pharm. 2022 Feb 18;79(Suppl 1):S13-S20. doi: 10.1093/ajhp/zxab382.

  PMID: 34597356 BACKGROUND

• Moussavi K, Nguyen LT, Hua H, Fitter S. Comparison of IV Insulin Dosing Strategies for Hyperkalemia in the Emergency Department. Crit Care Explor. 2020 Apr 29;2(4):e0092. doi: 10.1097/CCE.0000000000000092. eCollection 2020 Apr.

  PMID: 32426734 BACKGROUND

• LaRue HA, Peksa GD, Shah SC. A Comparison of Insulin Doses for the Treatment of Hyperkalemia in Patients with Renal Insufficiency. Pharmacotherapy. 2017 Dec;37(12):1516-1522. doi: 10.1002/phar.2038. Epub 2017 Nov 27.

  PMID: 28976587 BACKGROUND

• Julious SA. Sample sizes for clinical trials with normal data. Stat Med. 2004 Jun 30;23(12):1921-86. doi: 10.1002/sim.1783.

  PMID: 15195324 BACKGROUND

• Humphrey TJL, James G, Wilkinson IB, Hiemstra TF. Clinical outcomes associated with the emergency treatment of hyperkalaemia with intravenous insulin-dextrose. Eur J Intern Med. 2022 Jan;95:87-92. doi: 10.1016/j.ejim.2021.09.018. Epub 2021 Oct 5.

  PMID: 34625340 BACKGROUND

• Garcia J, Pintens M, Morris A, Takamoto P, Baumgartner L, Tasaka CL. Reduced Versus Conventional Dose Insulin for Hyperkalemia Treatment. J Pharm Pract. 2020 Jun;33(3):262-266. doi: 10.1177/0897190018799220. Epub 2018 Sep 6.

  PMID: 30189765 BACKGROUND

• Finder SN, McLaughlin LB, Dillon RC. 5 versus 10 Units of Intravenous Insulin for Hyperkalemia in Patients With Moderate Renal Dysfunction. J Emerg Med. 2022 Mar;62(3):298-305. doi: 10.1016/j.jemermed.2021.10.027. Epub 2022 Jan 17.

  PMID: 35058093 BACKGROUND

• Chothia MY, Humphrey T, Schoonees A, Chikte UME, Davids MR. Hypoglycaemia due to insulin therapy for the management of hyperkalaemia in hospitalised adults: A scoping review. PLoS One. 2022 May 12;17(5):e0268395. doi: 10.1371/journal.pone.0268395. eCollection 2022.

  PMID: 35552566 BACKGROUND

Related Links

• UKKA Clinical Practice Guideline - Management of Hyperkalaemia in Adults - October 2023

MeSH Terms

Conditions

Hyperkalemia; Hypoglycemia

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Glucose Metabolism Disorders

Study Officials

• NURUL ELLMY ABDUL RAZAK, MBBCh

  University of Malaya

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Emergency Physician

Study Record Dates

• First Submitted: December 6, 2024
• First Posted: December 9, 2024
• Study Start: April 20, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Beginning 3 months and ending 3 years after the publication of results
• Access Criteria: De-identified Individual Participant Data (IPD), including demographic data, serum potassium levels, blood glucose levels, and treatment outcomes, will be shared with qualified researchers who submit a scientifically sound proposal. Researchers must provide detailed objectives, planned analyses, and compliance with ethical and privacy standards. Study Protocol and Informed Consent Form (ICF) will be available upon request. Proposals should be submitted via email to the Principal Investigator.

Locations

MY (1)