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
Trial Snapshot
- Phase
- Not Applicable
- Status
- Enrolling By Invitation
- Sponsor
- University of Malaya
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Mean potassium difference between baseline and 1 hour post therapy
Study Overview
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.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 100 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
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.
Intervention: Conventional Dose Therapy (Procedure)
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.
Intervention: Lower Dose Therapy (Procedure)
Outcomes
Primary Outcomes
Mean potassium difference between baseline and 1 hour post therapy
Time Frame: From administration of actrapid to the first hour after administration of actrapid
The difference in serum potassium level between baseline and one hour post therapy will be compared between the two arms
Secondary Outcomes
- 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)
Investigators
Dr. Khadijah Poh Yuen Yoong
Consultant Emergency Physician
University of Malaya