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

NCT ID: NCT06724991

Last Updated: 2024-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-01-01

Study Completion Date

2027-06-01

Brief Summary

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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.

Detailed Description

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The primary research question that guided the design of this study arose from the consideration of optimizing insulin and dextrose dosing in the management of mild to moderate hyperkalaemia, specifically in patients with serum potassium levels below 6.4 mmol/L. This focus acknowledges that severe hyperkalaemia necessitates higher insulin doses, often accompanied by a corresponding increase in dextrose, to achieve a rapid and significant reduction in serum potassium levels. However, the necessity of administering the full conventional dose of insulin and dextrose in moderate hyperkalaemia is still unclear. Investigators hypothesize that a lower dose regimen may achieve similar efficacy in reducing serum potassium levels while potentially minimizing the risks associated with higher doses, such as hypoglycaemia and extravasation injury.

Previous studies have reported reductions in potassium ranging from 0.6-1.17 mmol/L following administration of lower dose of insulin. In this study, investigators aim to assess whether lower doses of insulin and dextrose are non-inferior to the standard dosing regimen. The non-inferiority margin has been defined as a reduction in serum potassium by 0.5 mmol/L for both treatment groups. This margin was carefully selected because a 0.5 mmol/L decrease in potassium is clinically significant, shifting the condition from moderate to mild hyperkalaemia, thereby reducing the risk of life-threatening arrhythmias. This threshold prioritises patient safety while potentially minimising adverse events, particularly hypoglycaemia, commonly linked to higher insulin doses.

Furthermore, if the lower doses are shown to be non-inferior, adverse events such as hypoglycaemia and extravasation could be reduced, enhancing the safety profile of hyperkalaemia management. This improvement represents a key secondary objective of the study and underscores the broader potential of dose optimisation.

Research specifically addressing optimal insulin dosing for hyperkalaemia is limited. Given limited research on optimal insulin dosing for hyperkalaemia, these findings could inform clinical guidelines, encouraging flexible, evidence-based dosing strategies in emergency and critical care settings

To determine the required sample size for this non-inferiority study comparing insulin dosages for treating moderate hyperkalaemia in the emergency department, investigators utilized a sample size calculation based on the method by Julious, 2004 and the following parameters.

Investigators aimed to detect whether the mean difference between the standard treatment and the experimental treatment does not exceed the non-inferiority limit of 0.5 mmol/L, with 80% power and a significance level of 0.05 for a two-sided test. Estimating a standard deviation of 0.68 mmol/L based on prior studies, and using the formula for comparing two means, 23 participants per arm are needed.

Including a 10% dropout rate, the total sample size required for the study is 50 participants, with 25 allocated to each treatment group.

Conditions

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Hyperkalemia

Keywords

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hyperkalemia hypoglycemia lower dose insulin extravasation injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Conventional Dose Therapy

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.

Group Type ACTIVE_COMPARATOR

Conventional Dose Therapy

Intervention Type 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.

Lower Dose Therapy

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.

Group Type EXPERIMENTAL

Lower Dose Therapy

Intervention Type 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.

Interventions

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Lower Dose Therapy

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.

Intervention Type PROCEDURE

Conventional Dose Therapy

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.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Malaya

OTHER

Sponsor Role lead

Responsible Party

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Dr. Khadijah Poh Yuen Yoong

Consultant Emergency Physician

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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NURUL ELLMY ABDUL RAZAK, MBBCh

Role: PRINCIPAL_INVESTIGATOR

University of Malaya

Locations

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University Malaya Medical Centre

Kuala Lumpur, , Malaysia

Site Status

Countries

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Malaysia

Central Contacts

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NURUL ELLMY MBBCh

Role: CONTACT

Phone: + 60173435391

Email: [email protected]

KHADIJAH POH MMed

Role: CONTACT

Email: [email protected]

References

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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.

Reference Type BACKGROUND
PMID: 38490803 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34167889 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22489323 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26416951 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34597356 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32426734 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28976587 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 15195324 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34625340 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30189765 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35058093 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35552566 (View on PubMed)

Related Links

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Other Identifiers

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RSCH ID-24-06414-1Q3

Identifier Type: OTHER

Identifier Source: secondary_id

2024101-14273

Identifier Type: -

Identifier Source: org_study_id