Comparative Efficacy of Insulin Aspart, Insulin Lispro, Glucose, and Salbutamol in Acute Hyperkalemia Management: A Randomized Clinical Trial

The primary objective of this study is to compare the efficacy of three treatment modalities—**insulin/dextrose** intravenous infusion, nebulized **salbutamol**, and a combination of nebulized salbutamol with insulin/dextrose intravenous infusion—in reducing serum potassium concentration at 60 minutes. This is evaluated as a first-line treatment for acute **hyperkalemia** in emergency department settings. The clinical relevance of this objective lies in its potential to inform optimal treatment strategies for rapid potassium reduction, which is critical in preventing life-threatening complications associated with hyperkalemia.

Secondary objectives include:

• Comparing the three treatment groups in terms of reducing serum potassium concentration at 180 minutes and 24 hours.
• Assessing the proportion of patients achieving normokalemia (4 to 4.9 mmol/l) at 60, 180 minutes, and 24 hours.
• Evaluating the proportion of patients requiring re-treatment or dialysis at 60, 180 minutes, and 24 hours.
• Comparing selected adverse effects at 60 and 180 minutes, including hypokalemia, hypomagnesemia, hypoglycemia, hyperglycemia, gastrointestinal disorders, tachycardia, and tremor.
• Analyzing the proportion of patients with heart rhythm disorders or high-grade atrioventricular block requiring urgent medication within the first 180 minutes, as observed on a standard 12-lead electrocardiogram.
• Comparing other ECG abnormalities at 60, 180 minutes, and 24 hours, such as auricular and ventricular extrasystoles, atrioventricular block, QRS interval prolongation, and QTc interval prolongation.
• Assessing the rates of major cardiovascular events at 60, 180 minutes, and 24 hours, including cardiac arrest, stroke, acute heart failure, complete atrioventricular block with ventricular rate under 30 bpm, ventricular fibrillation, and ventricular tachycardia.

The clinical trial focuses on patients with **hyperkalemia** and aims to evaluate the efficacy of different treatment modalities in reducing serum potassium levels in emergency settings. The study population includes both male and female participants, aged 18 years and older, who have been admitted to the emergency department. Participants must have a local laboratory serum potassium level of 5.5 mmol/l or higher and provide written informed consent prior to participation. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **insulin**/**dextrose** intravenous infusion, nebulized **salbutamol**, and their combination in reducing serum potassium levels in patients with **hyperkalemia**. This study is a randomized, controlled, double-blind trial, ensuring that neither the participants nor the investigators know which treatment the participants are receiving, thus minimizing bias. The trial is expected to span from December 20, 2019, to December 20, 2025, with the primary objective of assessing the mean change in serum potassium levels at 60 minutes post-treatment initiation.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (over 18 years), admission to the emergency department, and a serum potassium level of 5.5 mmol/l or higher. Written informed consent is required prior to participation. Following the screening, participants will be randomly assigned to one of the treatment groups. Follow-up visits will occur at 60 minutes, 180 minutes, and 24 hours post-treatment to monitor changes in serum potassium levels and assess secondary endpoints, including the proportion of patients achieving target potassium levels, the need for re-treatment or dialysis, and the occurrence of adverse effects or cardiovascular events.

The expected duration of participant involvement is approximately 24 hours, with conditions for early termination including withdrawal of consent or the occurrence of serious adverse events. The end-of-study visit will involve a final assessment of serum potassium levels and any adverse events experienced during the trial. The trial's primary endpoint is the mean change in serum potassium level from baseline to 60 minutes, while secondary endpoints include changes at 180 minutes and 24 hours, as well as the evaluation of safety and efficacy parameters.

The clinical trial involves the administration of several treatments to evaluate their efficacy in reducing serum potassium concentration in patients with acute hyperkalemia. The first experimental medication is **NovoRapid**, a **solution for injection** containing **insulin aspart**. It is provided in vials with a concentration of 100 units/ml. The medication is administered via **intravenous use** with a maximum daily dose of 10 units. The treatment period is limited to one day, and participant compliance is monitored through standard clinical trial procedures.

Another experimental treatment used in the trial is **Humalog**, which is also a **solution for injection** containing **insulin lispro**. Similar to NovoRapid, it is available in vials with a concentration of 100 units/ml and is administered intravenously. The maximum daily dose is 10 units, and the treatment duration is restricted to one day. Compliance monitoring is conducted to ensure adherence to the dosing schedule.

The trial also includes the administration of **GLUCOSE** as a non-experimental treatment. This **solution for injection** is used as a comparator and is administered intravenously. The maximum daily dose is 500 ml, with the treatment period limited to one day. The glucose solution serves as a standard-of-care therapy in the management of hyperkalemia.

Additionally, the trial incorporates the use of **SALBUTAMOL ARROW** and **SALBUTAMOL VIATRIS**, both of which are **nebuliser solutions** containing **salbutamol** and **salbutamol sulfate**, respectively. These medications are administered via **inhalation use**. Each has a maximum daily dose of 10 mg, with the treatment period limited to one day. The administration of these nebuliser solutions is monitored to ensure proper dosing and participant compliance.

The efficacy of the clinical trial titled "InSaKa trial: Insulin dextrose infusion versus nebulized salbutamol versus combination of salbutamol and insulin dextrose in acute **hyperkalemia**: a randomized clinical trial" will be assessed through a series of primary and secondary endpoints. The primary endpoint is the mean change in the absolute serum potassium level from baseline to 60 minutes, measured in mmol/l. This endpoint is critical for evaluating the immediate effect of the treatments on serum potassium concentration.

Secondary endpoints include the mean change in serum potassium level from baseline to 180 minutes and 24 hours, and the proportion of patients achieving a serum potassium level of 4 mmol/l to less than 4.9 mmol/l at 60, 180 minutes, and 24 hours. Additionally, the trial will assess the proportion of patients requiring re-treatment or dialysis, the occurrence of adverse effects, heart rhythm disorders, high-grade atrioventricular block requiring urgent medication, electrocardiographic abnormalities, and major cardiovascular events at specified time points of 60, 180 minutes, and 24 hours.

The efficacy parameters will be collected and analyzed at these specific time points to determine the effectiveness of the interventions in reducing serum potassium levels and managing associated clinical outcomes. The trial aims to provide comprehensive data on the comparative efficacy of the treatment options in the emergency department setting for patients with acute hyperkalemia.