Clinical trial NCT06036823: 5 Versus 10 Units of Insulin in Hyperkalemia Management
Official title: 5 Versus 10 Units of Insulin in Hyperkalemia Management: Multi-center, Prospective, Double-blind, Non-inferiority, Randomized Control Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Hyperkalemia
Potassium Imbalance
Electrolyte Imbalance
Electrolyte Disturbance
Keywords: insulin
hyperkalemia
hypoglycmiea
anti-hyperkalemia
electrolytes abnormalities
Lead sponsor: Oman Medical Speciality Board
Sponsor class: OTHER_GOV
Collaborators: name: Sultan Qaboos University
First posted: 2023-09-14
Enrollment: 336
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: the study group will receive 5 units of intravenous insulin control group will receive 10 unites of IV insulin
Primary purpose: TREATMENT

Brief summary: The goal of this study is to compare 5 units of intravenous Regular insulin to 10 units of intravenous regular insulin in the management of hyperkalemia. We will measure the efficacy of these 2 doses of insulin in reducing hyperkalemia at 2 hours from administration using the main laboratory serum values.

Detailed description: Introduction: Hyperkalaemia is a serum Potassium (K) level of more than 5.5 mEq/L. It is a common emergency medicine presentation and can be life-threatening. Because of the emergency in correcting hyperkalemia, different medications are used to reduce high potassium levels to normal as soon as possible. Salbutamol inhalers, Glucose solutions, and Insulin are the main medications for managing hyperkalemia. Insulin and Dextrose shift potassium ions into body cells by stimulating the sodium/potassium ATP pump. Its effect starts in less than fifteen minutes and can last up to sixty minutes. It usually reduces potassium up to 1.1 mEq/l. There are different recommendations for Insulin dose and rate of administration for patients with hyperkalemia.

Method: This will be a multi-center, prospective, double-blind, non-inferiority, randomized control trial. 336 hyperkalemia patients will be randomized to the intervention group 5 units of intravenous Regular insulin and 10 units of intravenous insulin groups with fifty ml of Dextrose Fifty percent. They will be enrolled once their potassium level is 5.5mEq/L or more. The attending physician and patient will be blinded about the dose of insulin that the patient received. Serum potassium will be measured at 0 and at 120 minutes from the start of the medications. Random blood glucose will be measured at 0, 60, and 120 minutes by Glucometer. The safety of our patients will be assessed by documentation of all adverse events, vital signs, and clinical assessment before and after drug administration. The study will end at 2 hours from insulin administration.

Aim: Our research idea aims to compare two recommended doses of Insulin (5 Units vs. 10 Units of Regular insulin given intravenously over thirty minutes) in the management of patients with hyperkalemia.

Primary objective: Mean reduction in serum potassium level using the main laboratory results at two hours from medication administration.

Secondary objectives: effect of initial (baseline) potassium level on the mean potassium reduction, and frequency of hypoglycemia between the 2 groups. Does the initial (baseline) blood glucose level will affect the function of insulin/dextrose in lowering potassium levels?

Patient Population: Adult patients (Aged 18 years and older) who present to the Emergency department at Sultan Qaboos University and Royal Hospital for evaluation and are found to have potassium levels of 5.5 mEq/L and above.

Intervention: Single dose of 5 units of intravenous insulin over 30 minutes with 50 ml of Dextrose 50%.

Clinical Measurement: Mean reduction of potassium level using the main laboratory results at 2 hours from insulin/dextrose administration. Hypoglycemia will be followed by a bedside glucometer.

Outcome: reduction of potassium level at 2 hours from medication administration and medication safety.

Eligibility criteria: Inclusion Criteria:

* Hyperkalemia patients with lab potassium levels equal to or more than 5.5 mEq/L (≥ 5.5 mEq/L)+.
* Adult: age 18 years or more.
* Agreed to participate in the study.

  * If an investigator decides to start anti-hyperkalemia medications based on the VBG/ABG patient can be enrolled but if the main laboratory value is less than 5.5 mEq/L patients will be excluded

Exclusion Criteria:

* Cardiac arrest
* Hyperglycemia with random blood sugar 20 mmol/L (13) or with acute diabetic complications like Diabetic Ketoacidosis / Hyperosmolar Hyperglycemic State.
* Hypoglycemia with random blood sugar (RBS) ≤ 3.89 mmol/l in Diabetic patients and less than 3 mmol/l in non-diabetic patients.
* Allergies for any medication in the protocol.
* Pregnancy.
* Hemolyzed potassium level as reported by the main lab.
* Hemolysis, Tumor lysis syndrome, or Rhabdomyolysis due to the ongoing release of potassium.
* Acidosis with a pH less than 7.1 will require Sodium bicarbonate (NaHO3).
* A patient who will need urgent Furosemide (Lasix), and or dialysis during the study period of 2 hours.
* Refused to participate.

Primary outcomes:
measure: To study the efficacy of two intravenous insulin doses (5 units and 10 units) in reducing serum potassium level in patients receiving hyperkalemia treatment using the main laboratory measurements. (the aim of reduction of 0.6 mmol/l +/- 0.2 mmol/L) (1).
timeFrame: At 2 hours from administration of medications
Secondary outcomes:
measure: Study the mean difference of the response to the anti-hyperkalemic measures based on the level of initial potassium (serum potassium before given any medications - At baseline).
timeFrame: 2 hours from administration of medications
measure: Association of mean potassium reduction with initial blood sugar level on potassium reduction
timeFrame: 2 hours from administration of medications
measure: Incidence of hypoglycemia (random blood sugar (RBS) ≤ 3.89 mmol/l in Diabetic patients and less than 3 mmol/l in non-diabetic patients) (12) and risk factor Characteristics of patients with a higher risk of developing hypoglycemia
timeFrame: 2 hours from administration of medications
Other outcomes:
Locations:
city: Seeb
country: Oman
facility: Sultan Qaboos University hospital
state: Muscat
Study officials:
affiliation: Sultan Qaboos University hospital
name: Suad Al-Abri
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Ron M. Walls, MD. Hyperkalemia. Rosen emergency medince Concepts and Clinical practice. 9th. Philadelphia : Elsevier, 2018, 117, pp. 1516 - 1519.
citation: Judith E. Tintinalli, MD, MS. Hyperkalemia. Tintinalli's Emergency Medicine a comprehensive study guide. 9th. s.l. : McGraw-Hill Education, 2020, 17, p. 89.
citation: McNicholas BA, Pham MH, Carli K, Chen CH, Colobong-Smith N, Anderson AE, Pham H. Treatment of Hyperkalemia With a Low-Dose Insulin Protocol Is Effective and Results in Reduced Hypoglycemia. Kidney Int Rep. 2017 Oct 24;3(2):328-336. doi: 10.1016/j.ekir.2017.10.009. eCollection 2018 Mar.
citation: 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.
citation: 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.
citation: Moussavi K, Garcia J, Tellez-Corrales E, Fitter S. Reduced alternative insulin dosing in hyperkalemia: A meta-analysis of effects on hypoglycemia and potassium reduction. Pharmacotherapy. 2021 Jul;41(7):598-607. doi: 10.1002/phar.2596. Epub 2021 Jun 1.
citation: Harel Z, Kamel KS. Optimal Dose and Method of Administration of Intravenous Insulin in the Management of Emergency Hyperkalemia: A Systematic Review. PLoS One. 2016 May 5;11(5):e0154963. doi: 10.1371/journal.pone.0154963. eCollection 2016.
citation: 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.