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

Официальное название

Efficacy Of Lower-Dose Versus Conventional-Dose Of Insulin And Dextrose For Treatment Of Mild And Moderate Hyperkalaemia In Emergency Department: A Randomised, Triple-Blinded, Non-Inferiority Trial

Обзор

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.

Подробное описание

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.

Вмешательства

• Процедура 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.
• Процедура 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.

Первичные конечные точки

• Mean potassium difference between baseline and 1 hour post therapy [Срок оценки: From administration of actrapid to the first hour after administration of actrapid]

Вторичные конечные точки (3)

• Incidence of hypoglycaemia within 6 hours of insulin administration [Срок оценки: 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 [Срок оценки: From administration of actrapid until the 6 hours after administration of actrapid]
• Mortality in patients within 7 days [Срок оценки: From enrolment to 7 days after receiving interventional treatment]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Малайзия · 1 центр

• University Malaya Medical Centre — Kuala Lumpur

Публикации

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT06724991 · 2024101-14273 · RSCH ID-24-06414-1Q3

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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