5 Versus 10 Units of Insulin in Hyperkalemia Management: Multi-center, Prospective, Double-blind, Non-inferiority, Randomized Control Trial.
Phase: PHASE4
Conditions: Hyperkalemia, Potassium Imbalance, Electrolyte Imbalance, Electrolyte Disturbance
Sponsor: Oman Medical Speciality Board

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Study protocol 
Title: 
5 versus 10 units of insulin in hyperkalemia 
management: Prospective, Double blinded, 
randomized controlled trial, multicentre, non-
inferiority. 
(5/10 trial) 
 
Principal investigator: 
Dr. Adnan Hussein Al-Ajmi ,  Oman medical speciality board, Emergency medicine resident. 
Dr. Ibrahim Sabri Al-Hooti,  Oman medical speciality board,  Emergency medicine resident. 
 
Authors: 
Dr. Usama Al-Khalasi, Oman medical speciality board,  Emergency medicine resident. 
Dr. Suad Abdullah Al-Abri, Emergency medicine,  senior consultant Sultan Qaboos University 
Hospital. 
Dr. Abdullah Al Reesi, Emergency medicine,  senior consultant Sultan Qaboos University Hospital 
Dr. Saif Al-Ghafri, Emergency medicine,  Consultant Sultan Qaboos University Hospital. 
Dr. Ali Al-Lawati, Internal medicine, Nephrology Consultant, Sultan Qaboos University Hospital.  
Dr: Abulmonim Al-Farsi, Emergency medicine, consultant, Royal hospital. 
 
 
 
 
 
 
Corresponding Author: Dr. Suad Abdullah Al-Abri. 
 
 
 
 
Ethical approval:   
- Medical Research Ethics Committee (MREC), College of Medicine and Health Sciences, 
Sultan Qaboos University, MREC#2779. Date:1st june 2022. 
- Sultanate of Oman, Ministry of Health Directorate General of Planning & Studies Centre of 
Studies and Research: MOH/CSR /23/26349. Date: 14/05/2023. 
 
 
 
Version number: 003.  
Date: 10/08/2023 
 
 

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Contents 
1. 
Summary: _____________________________________________________________ 4 
2. 
Introduction: literature review and justification of the study. ____________________ 5 
The gap in the studies: ___________________________________________________________ 5 
3. 
Objectives and hypothesis of the study: ______________________________________ 6 
Primary outcome: _______________________________________________________ 6 
Secondary outcome ______________________________________________________ 6 
Study hypothesis _______________________________________________________________ 7 
4. 
Feasibility of the study ___________________________________________________ 7 
5. 
Research Design and Methods ____________________________________________ 7 
Study design ___________________________________________________________________ 7 
Characteristics of study area and target population ___________________________________ 7 
Control Group __________________________________________________________ 7 
Intervention Group ______________________________________________________ 7 
Primary and secondary endpoints _________________________________________________ 8 
Primary endpoint: _______________________________________________________ 8 
Secondary endpoint: _____________________________________________________ 8 
Selection and withdrawal of subjects: ______________________________________________ 8 
Inclusion and exclusion criteria ____________________________________________ 8 
Withdrawal criteria ______________________________________________________ 8 
Sampling and sample size _________________________________________________ 9 
6. 
Randomization _________________________________________________________ 9 
7. 
Study flow _____________________________________________________________ 9 
8. 
Study treatment. _______________________________________________________ 11 
Medications for study treatment. _________________________________________________ 11 
Regular insulin/ Dextrose 50% ____________________________________________ 11 
Method for Application of Intravenous Regular Insulin 5 units __________________________ 11 
Method for Application of Intravenous Regular Insulin 10 units _________________________ 11 
Salbutamol ___________________________________________________________________ 12 
Method for Application of Salbutamol Nebulization ___________________________ 12 
9. 
Storage, Handling, and Administration ____________________________________ 12 
Packaging and Labelling _________________________________________________________ 12 
10. 
Variable definitions and measurements __________________________________ 13 
Data collection tools and methods ________________________________________________ 13 
Data quality __________________________________________________________________ 13 
Data analysis _________________________________________________________________ 13 
11. 
Ethical considerations ________________________________________________ 13 

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12. 
Conflict of interest: __________________________________________________ 13 
13. 
Incentives: _________________________________________________________ 14 
14. 
Results Dissemination ________________________________________________ 14 
15. 
Management and monitoring of the research activities: _____________________ 14 
16. 
Limitations and difficulties of the study: _________________________________ 14 
17. 
Safety Assessments ___________________________________________________ 14 
Adverse Events ________________________________________________________________ 14 
18. 
Rationale for subject selection and recruitment. ___________________________ 15 
19. 
Efficacy and safety assessment. _________________________________________ 15 
Efficacy Variables ______________________________________________________________ 15 
Primary Efficacy Variable _______________________________________________ 15 
Secondary Efficacy Variables _____________________________________________ 15 
Safety Variables _______________________________________________________ 15 
20. 
Statistical analysis: ___________________________________________________ 15 
Subgroup analyses planned. _____________________________________________________ 15 
Number of subjects to be enrolled.________________________________________________ 15 
Rationale for the choice of sample size ____________________________________________ 16 
Planned interim analyses. _______________________________________________________ 16 
21. 
Criteria for terminating the study. _______________________________________ 16 
22. 
Quality control and quality assurance. ___________________________________ 16 
Preparation quality ____________________________________________________________ 16 
23. 
Data handling and record keeping. ______________________________________ 17 
24. 
Procedures for reporting deviations from the original plan. __________________ 18 
Study Protocol Violation Algorithm: _______________________________________________ 19 
Anticipated Protocol Violations: __________________________________________________ 20 
25. 
Anticipated results ___________________________________________________ 20 
26. 
References: _________________________________________________________ 21 
27. 
Appendix: __________________________________________________________ 23 
Data collection sheet ___________________________________________________________ 23 
Written informed consent ________________________________________________ 24 
Withdrawal form ______________________________________________________________ 27 
Medications administration form: ________________________________________________ 28 
Study Flow chart: ______________________________________________________________ 29 
Hypoglycemia management flow chart ____________________________________________ 30 
Ministry of Health hyperkalemia management: _____________________________________ 31 
Serious Adverse Event Case Log __________________________________________________ 33 

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Subject Deviation/Unanticipated Problem Case Log __________________________________ 34 
 
 
1. Summary: 
 
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/ investigator 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. We will follow serum potassium by blood 
sampling. Hypoglycemia will be followed by a bedside glucometer. 
Outcome: reduction of potassium level at 2 hours from medication administration and 
medication safety. 
 
 
 
 
 

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2. Introduction: literature review and justification of the study. 
 
Hyperkalaemia is the most dangerous and deadly electrolyte imbalance seen in all health 
institutions (1).  Potassium is mainly an intracellular cation. The normal level of potassium is 
between 3.5 to 5.5 mEq/L (12). It is critical to identify and manage hyperkalemia as soon as 
possible. Hyperkalaemia can affect multiple systems including the central and peripheral 
nervous system, gastrointestinal system, renal system, and neuromuscular system including 
the cardiac muscles (2) The most dangerous effect of hyperkalemia is cardiac toxicity. 
Hyperkalaemia affects the heart by depressing it is electrical and muscular functions leading 
to cardiac arrhythmia and sudden cardiac death (1).  
Potassium plasma level is determined by three main factors: the amount of potassium intake, 
the distribution of plasma between the extracellular fluid and the cells, and potassium 
excretion with urine (3). 
There are different medications used for the treatment of hyperkalemia. The known regimen 
has 3 components (1) (4). The 1st group of treatment is cardiac muscle-stabilizing agents like 
Calcium gluconate (1) (4). The 2nd group is the medications that shift Potassium from the 
plasma to inside the cells like Insulin and Salbutamol (1) (4). The 3rd group of treatments is 
the ones that eliminate potassium from the body like dialysis and diuretics (1) (4).  The 
standard dose of insulin is 10 units of Regular insulin as a bolus with dextrose 50% 50 to 100 
ml (1) (4) (5). Some guidelines recommend an insulin dose between 5-10 units of Regular 
insulin as a bolus (2). 
There are multiple studies done to monitor the efficacy and safety of potassium-lowering 
agents like insulin and other medications. A recent retrospective cohort study showed no 
difference between 5 Units and 10 units in lowering potassium levels (6).  
Most of the studies done to compare insulin doses were retrospective studies and most of 
them were done on a patient with renal insufficiency (acute and chronic). These studies 
showed no difference in the efficacy of lowering potassium levels between 5 units of insulin 
and 10 units of insulin. They showed 5 units of insulin have the advantage of fewer 
hypoglycemia events compared to 10 units. As Bairbre A. McNicholas et al 2017,  Heather A 
LaRue 2017, and Kayvan Moussavi 2021 (7) (8) (9) (10) showed the same finding  
 
Ziv Harel and Kamel S. Kamel 2016 in their systemic review of articles that looked into the 
different doses  of insulin found no difference in the efficacy of lowering potassium between 
10, 12, and 20 units of insulin (11) 
 
Kayvan Moussavi et al 2020 in their observation study showed that less than 10 units of 
insulin cause less incidence of hypoglycemia but the amount of potassium reduction was less 
in patients who received less than 10 units (8). But this study was a retrospective for patients 
who attended the emergency department in a single center. Although they mentioned less 
than 10 units have less efficacy but the doses of less than 10 units range from 3 units to 8 
units as it will be difficult to conclude this range of values. (8). 
The gap in the studies: 
From these studies our question came. If 5 units of intravenous regular insulin reduce 
potassium level as effective as 10 units of insulin with less hypoglycemia why we do not use 

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it as our standard dose to avoid a possible complications and will be less cost as half the dose 
of insulin will be used in the future as standard. 
Most of the studies were retrospective studies and a lot of confounders may affect the result, 
that’s why this study will add much to the argument in regarding to the best dose in managing 
patient with hyperkalemia. Also the investigators will review the rate of hypoglycemia and 
who is more at risk to avoid this complication among those patients. In our secondary 
objective the investigators will analyse the effect of blood sugar level and potassium level in 
patient response to treatment. 
 
 
 
 
 
 
 
 
3. Objectives and hypothesis of the study: 
Primary outcome:  
1. 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).  Blood sample will be collected and send to the main laboratory for 
analysis at two hours from medications administration. The efficacy of the 2 doses 
will be measured at 2 hours from administration of medications by comparing the 
amount of changes in potassium level at two hours. 
Secondary outcome 
1. 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) (the investigators will categorize potassium level into groups mild (5.5–6 
mmol/l), moderate (6–6.5 mmol/l) and severe (>6.5 mmol/l) and will see the mean 
difference in reduction in potassium level in between the 2 doses).  
2. Association of mean potassium reduction with initial blood sugar level (blood sugar 
level before given any medications – At Baseline) on potassium reduction (the 
investigators will categorize blood sugar into groups: Below 10mmol/L, 10.1-14.9 
mmol/L, and 15 – 19.9mmol/L among each group the investigators will see the mean 
potassium reduction level).  
3. 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 
Characteristic of patients of higher risk of developing hypoglycemia (the investigators 
will investigate which group of patients will have a high risk of hypoglycemia ((e.g: 
initial Glucose level, initial creatinin/renal function, comorbidities, type of 
dialysis…).  

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Study hypothesis 
No difference between 5 and 10 units of intravenous regular insulin in lowering potassium 
levels in patients with hyperkalemia at 2 hours.  
4. Feasibility of the study 
As hyperkalemia is very common our investigators can find a good number of cases. Also, it 
will be a multicentre study with the inclusion of emergency department patients in the study. 
The American College of Emergency Physicians (ACEP) recommends the use of both 5 units 
and 10 units of insulin as treatment of hyperkalemia published on their anti-hyperkalemia 
protocol in 2021 (13). With an average of 1 patient per day, the research team can achieve the 
target sample size within the timeline. Funding will be requested from the research council 
(Ministry of Higher Education, Research and Innovation) and Sultan Qaboos University fund.  
5. Research Design and Methods 
Study design 
Prospective double blinded, randomized controlled clinical trial, in adults (from age 18) who 
presents to the  emergency department (ED) at Sultan Qaboos University Hospital, and Royal 
Hospital, with hyperkalemia (potassium level >5.5 mEq/l, Written consent will be obtained 
from the  patient. Eligible subjects will be enrolled (Appendix: Written informed consent). 
Characteristics of study area and target population 
This study will be conduct in 2 different hospitals, Sultan Qaboos University Hospital and 
Royal Hospitals both are tertiary hospitals in Muscat region. The research team might extend 
to other hospitals if noticed that we are short on patient number. Patient will be selected 
based on the potassium level in the main laboratory report. When potassium level ≥ 5.5 
mEq/l the patient will be screened for inclusion and exclusion criteria. Our 5.5 mEq/l lab cut 
off came from Ministry of health protocol (see appendix: Ministry of health hyperkalemia 
management protocol) and ACEP protocol for hyperkalemia management (13). 
Control Group  
The patient will receive 10 U of regular insulin + Dextrose 50% over 30 minutes + 
salbutamol nebulization 10mg in 3ml normal saline over 15min, calcium gluconate will be 
given according to the physician responsible about the case. 
Intervention Group 
The patient will receive 5 U of regular insulin + Dextrose 50% over 30 minutes + salbutamol 
nebulization 10mg in 3ml normal saline over 15min, calcium gluconate will be given 
according to the physician responsible about the case. 

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Primary and secondary endpoints 
Primary endpoint:  
 
Mean reduction in serum potassium level at 2 hours from insulin administration. 
Blood sample from the patient will be obtained for potassium measurement. The 
samples will be sent to the main laboratory for potassium level analysis. 
Secondary endpoint: 
 
Mean difference of the response to the antihyperkalemic measures based of the 
baseline level of potassium.  
 
Incidence of hypoglycemia and risk factors characteristic of patients of higher risk of 
developing hypoglycemia.  
 
Association of mean potassium reduction with baseline blood sugar level. 
Selection and withdrawal of subjects:  
Inclusion and exclusion criteria 
Inclusion criteria: 
 Hyperkalemia patients with lab potassium levels equal to or more than 5.5 mEq/L (≥ 
5.5 mEq/L)*.  
 Adult: aged 18 years or more.  
 Agreed to participate in the study.  
* If a doctor/Investigator decided 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.  
Withdrawal criteria  
A subject/patient may be withdrawn from the study at any time for any reason and 
without penalty or prejudice.  The following situations may be cause for a subject to 
be withdrawn from the study:  
• Subject did not fulfil the inclusion or exclusion criteria.   

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• Subject experienced a significant complication, deemed due to the 
study treatment.  
• Subject developed an inter-current illness, condition, or procedural 
complication that would interfere with continued participation.   
• Subject voluntarily withdrew consent.   
• Subject was in violation of the protocol.  
• Treating Physician decided it is in the best medical interest of 
the subject to terminate involvement.  
Upon occurrence of a serious adverse event or intolerable adverse event, the principal 
investigator will be notified. If a subject is discontinued from study treatment due to a serious 
adverse event, the event will be followed until resolution. The investigational staff must fill 
the withdrawal form (Appendix: Withdrawal form). 
Sampling and sample size 
Our target will be all patients with hyperkalemia presenting to the emergency departments in 
both hospitals. The Sample size was calculated based on a study published in Critical Care 
Explorations Journal 2020 with the article named Comparison of IV Insulin Dosing Strategies 
for Hyperkalemia in the Emergency Department by Kayvan Moussavi et al (8). The 
anticipated effect size d = 0.2 with alpha error prob = 0.0250 (one-side), actual power 90, 
Standard deviation of 0.62 and allocation ratio 1:1. The calculated sample size is 320 (160 in 
each arm). Our statistician estimated a 5% drop rate. So the sample size increasesd to 336 
(168 in each arm).  
6. Randomization 
When a patient has hyperkalemia (K ≥ 5.5 mEq/L) our doctor/investigator will come to 
explain the research to the patient/relatives and after explaining all details a written consent 
will be signed. Our doctor/investigator will take a random envelope from the study box to 
randomize the patient between 5 units or 10 units of insulin with 50 ml of 50% Dextrose and 
salbutamol Nebulization. The doctor will take the envelope code and place it on the data 
collection sheet without looking into the instructions. The Doctor will give the nurse that 
envelope. Each envelope will have instructions about the medications administration route 
and dose (see appendix: medications administration form). The Nurse will administer the 
medications with the documentation of starting time. Then our doctor will follow the patients 
and lab results for 2 hours based on the ACEP and Ministry of Health/Royal hospital 
protocol.  
Randomization codes will be done by an online free site for having unique codes 
(https://www.randomcodegenerator.com/en/generate-codes). 
Eligible 
participants 
after 
obtaining consent will be randomly assigned to either 5 units of Intravenous insulin or 10 
units of intravenous insulin. The researcher and patient will not know the dose of insulin 
administered.  
7. Study flow 
The study protocol will be for a total of 2 hours. All groups will follow the same path except 
the dose of insulin administered. After the result of potassium level (≥ 5.5 mEq/L) patient 
will be screened for inclusion and exclusion criteria at the same time all other medications 
except insulin can be administered as the doses are fixed. Eligible patient will have to sign a 

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written consent if they agreed to be involved in our study. The initial data and basic labs will 
be collected before starting the study protocol. The incharge doctor/investigator will take the 
random code  and write it on the data collection sheet of that patient from already prepared 
list/code and give the assigned nurse the medications administration card/form (see appendix: 
medications administration form).  
Every patient will receive:  
o Potassium lowering agent: 
 Intravenous Regular insulin 5 units OR 10 units with Glucose 
50% water 50 ml over 30 minutes according to the 
randomization.  
 Salbutamol nebulization 10 mg in 3ml normal saline over 15 
minutes. 
o The physician will decide the need of cardiac stabilizing agents (e.g 
Calcium Gluconate) as indicated by the physician in-charge of the 
patient. 
- 
Please see study flow chart in the attachment. 
5 Units insulin group 
10 units insulin group 
Medications  to be administered: 
•
IV Insulin Regular 5 units with Dextrose 
50 % 50 ml over 30 minutes. 
•
Salbutamol  10 mg NEB over 15 minutes. 
 
Medications  to be administered: 
•
IV Insulin Regular 10 units with Dextrose 
50 % 50 ml over 30 minutes. 
•
Salbutamol  10 mg NEB over 15 minutes. 
 
Figure 1: Treatment. RBS: Random Blood sugar. IV: Intravenous. NEB: Nebulization. 
 
Initial investigations will include:  
ECG, Urea and electrolytes, Creatinine, eGFR, Random blood sugar, complete blood 
count, Magnesium level, bone profile, phosphate level,  will be attached if not sent 
before. 
Repeated labs will be with these frequencies: 
Potassium level: 0 and 120 minutes from medications administration 
time. 
Blood sugar: 0, 60 and 120 minutes from medications administration 
time. 
The study will be over at 2 hours (120 minutes) or by patient decision to withdraw from the 
study. 
 

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8. Study treatment.  
Medications for study treatment. 
Regular insulin/ Dextrose 50% 
Subjects in the emergency department with hyperkalemia will be administered regular insulin 
either 5 units or 10 units. 
After identifying appropriate adult patients, obtaining written consent (Appendix: Written 
Informed consent), and labs confirmed that patient is having hyperkalemia. antihyperkalemic 
measures will be started, Regular insulin (5units or 10units) will be administered according to 
the steps below. 
Method for Application of Intravenous Regular Insulin 5 units  
1. Preform hand hygiene and don clean gloves.  
2. Draw the 5 units of regular insulin.  
3. Mix it with 50ml of dextrose 50%.  
4. Connect to placed venous cannula.  
5. Run it no less than 5 seconds (proposed 30 minutes)  
6. Disconnect and discard all materials in their proper disposal bins.  
7. Remove gloves and preform hand hygiene.  
Method for Application of Intravenous Regular Insulin 10 units  
1. Preform hand hygiene and don clean gloves.  
2. Draw the 10 units of regular insulin.  
3. Mix it with 50ml of dextrose 50%.  
4. Connect to placed venous cannula.  
5. Run it no less than 5 seconds (proposed 30 minutes)  
6. Disconnect and discard all materials in their proper disposal bins.  

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7. Remove gloves and preform hand hygiene.  
Salbutamol  
Method for Application of Salbutamol Nebulization  
1. Preform hand hygiene and don clean gloves.  
2. Take 10 mg of insulin. 
3. Mix it with 3 ml of Sodium Chloride 0.9%.  
4. Put it on Nebulization devise.  
5. Run it for 15 minutes 
6. Disconnect and discard all materials in their proper disposal bins.  
7. Remove gloves and preform hand hygiene.  
9. Storage, Handling, and Administration  
The principle investigator and co-investigators will ensure that:  
• The study treatment is handled and stored safely and properly.  
• The study treatment is only dispensed to study subjects in 
accordance with the protocol.  
• The study treatment will be stored in accordance to product 
labelling.   
o Exposure to light, freezing and extreme heat should be avoided.   
  O Will Be stored the at pharmacy in controlled room temperature.  
• There will be only one use per ampule of treatment per subject.  
                 • The study treatment will be checked for expiration dates prior to use. 
Packaging and Labelling  
A calculated sample size equivalent both insulin doses 5 units VS 10 units will be prepared 
and set ready to  be used based on randomization blocks. Each package has its own unique 
number corresponding to (case and control) sampling.  
Each package contains:  
• Envelope with:  
o Data collection sheet with unique generated number.  
o Consent form.  
o Instructions sheet 
o Medication administration form (for the nurses). 
 
Blood investigation will be sent to biochemistry lab for potassium level and other 
investigations, and it’s the only acceptable way in the study. The study investigators will 
verify that study treatments are received intact and in the correct amounts.   

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10. Variable definitions and measurements 
Intravenous Regular Insulin will be used for our intervention. Potassium level will be 
measured by the main laboratory. Our outcome will be measured based on amount of 
potassium level reduction. 
 
 Hypoglycemia will be defined as (random blood sugar (RBS) ≤ 3.89 mmol/l in Diabetic 
patients and less than 3 mmol/l in non-Diabetic patients). 
Data collection tools and methods 
All data will be collected from the hospital information system. Data will be kept in secured 
files with encryption keys/password to maintain all patients’ privacy. Only who is involved in 
the study will be able to access the files. 
Data quality 
In each site there will be a focal point. A physician will be responsible for that site. Before 
the study starts our investigators will do training sessions about the study and will clarify all 
the details that the site physicians inquire. Research assistances will be hired for data 
collections to facilitate the process of data collection and to monitor the flow of the study 
protocol in each site. 
Data analysis 
Statistical Package for the Social Sciences (SPSS) applications version 29 will be used for 
our analysis.  
11. Ethical considerations 
Ethical approval will be needed from both hospitals before starting our research. Any 
adjustment advised by all ethical committees the research team will apply it to ensure patient 
safety. At any time during our study if the investigator noticed any increase risk on the 
patient safety the investigator will stop our study protocol. 
Because the study will not deviate from what is practiced by some physician and what is 
recommended by some guidelines our researchers team do not anticipate major harm on the 
patients. Even with this our investigator will follow our patients/participants and will stop the 
study if any indicator for harm rose at any time of the study. Our study will help if it proved 
no difference in the effect of both doses in 2 main things. The 1st one less hypoglycemia for 
the patients in the future and the 2nd main point cost effect as less doses of the same 
medication will be required to achieve the same goal. 
By the end of the study all participants will be contacted and our investigators will share the 
results with them and how their contribution helped the advancement of medical field. 
12. Conflict of interest: 
No conflict of interest 

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13. Incentives: 
No incentives of any kind will be given to the participants. 
14. Results Dissemination 
After completing the study the research team will publish the results in international journals 
and will have poster presentations. 
 
15. Management and monitoring of the research activities: 
The full team will manage the study flow. Each researcher will be responsible for a hospital 
work flow at a certain time then the researchers will swab after a period of time. Daily 
monitor will be done for all the cases via direct visit or follow up via the phone or Virtual 
meeting. Once enough sample collected the investigators will start our initial analysis of 
them. 
16. Limitations and difficulties of the study: 
The large sample size will need to be followed and all data must be kept and organised all 
time. 
Multicentre will have some difficulties as 2 different HIS used in these hospitals. 
Funding will be needed for to cover all the logistics and facilitate the flow of the 
research.. 
17. Safety Assessments  
Adverse Events  
All adverse events will be documented on serious adverse event case log. All 
serious adverse events should be immediately reported to the primary investigator. 
Any serious, adverse event will be reported immediately to the Institutional Review 
Board.  
An Adverse Events is considered serious if it causes a threat to the patient’s 
life or functioning.  The U.S. Food and Drug Administration (FDA) define a 
serious adverse event (SAE) as any untoward medical occurrence that:  
• Results in death.  
• Life threatening (places the patient at risk of death).  
• Requires hospitalization or prolongs an existing hospitalization.  
• Causes persistent or significant disability or incapacity.  
• Requires medical intervention to prevent one of the above outcomes.  

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18. Rationale for subject selection and recruitment.  
This is a prospective efficacy, safety and tolerability trial in adults. Active treatment 
(a single dose of intravenous insulin 5 units or 10 units) will be used. The population 
selected for this study, adult patients is a patient population that may benefit from 
the use of insulin. This is a population in whom intravenous 5 units of insulin has 
been approved for and in whom insulin has been shown to be safe and effective 
when used for hyperkalemia management, specifically renal failure patient. This is 
also a population in whom other dose insulin, 10 units of insulin have been shown to 
be efficacious and safe.  Therefore, it seems highly likely that the intravenous 5 
units of insulin, is an appropriate dose and it will also be effective, safe and well 
tolerated. 
 
19.  Efficacy and safety assessment.  
Efficacy Variables  
Primary Efficacy Variable  
The primary efficacy variable is the assessment of reduction of the potassium level 
after intravenous regular insulin dose (either 5 units or 10 units) at 2 hours from 
medication administration. Blood sample will be collected from the patient and will 
be sent to the main laboratory for analysis. 
Secondary Efficacy Variables  
The secondary efficacy measurement of risk of hypoglycemia event and the risk factors 
of hypoglycemia.  
Safety Variables  
The safety variables are the occurrence of adverse events. 
 
20. Statistical analysis:  
Subgroup analyses planned.  
No subgroup analyses planned.  
Number of subjects to be enrolled.  
336 subjects will be needed (168 in each arm).  

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Rationale for the choice of sample size   
The Sample size was calculated based on a study published in Critical Care Explorations 
Journal 2020 with the article named Comparison of IV Insulin Dosing Strategies for 
Hyperkalemia in the Emergency Department by Kayvan Moussavi et al (8). The anticipated 
effect size d = 0.2 with alpha error prob = 0.0250 (one-side), actual power 90, Standard 
deviation of 0.62 and allocation ratio 1:1. The calculated sample size is 320 (160 in each 
arm). Our statistician estimated a 5% drop rate. So the sample size increased to 336 (168 in 
each arm).  
Planned interim analyses.  
Interim analyses will be done after collecting 50% of the data. 
 
21. Criteria for terminating the study.  
A subject/Patient who is enrolled in the study and for whom study treatment is 
prematurely terminated will be discontinued from study treatment. After 
discontinuation/early release from the study, the subject/patient will receive 
standard-of-care treatment as per the treating clinician. End of Study Efficacy and 
Safety assessments will be performed, if appropriate and whenever possible.  
The study will be terminated when 336 subjects are enrolled, and all data is obtained 
and documented on the data collection sheet and transferred to Epi-Data program.   
22. Quality control and quality assurance.  
Preparation quality   
• A study approval from the Royal Hospital and Sultan Qaboos 
University hospital review board obtained.  
• Ensure that all required documents (data collection sheet, informed 
consent), randomization packages are in order and easily accessible 
for the investigators.   
o Investigator’s brochure  
      ▪ To document that relevant and current scientific information about 
the investigational product has been provided to the investigator.  
o Signed protocol.  
o Informed consent form.  
o Subject Deviation/Unanticipated Problem Case Log.  
o Serious Adverse Event (SAE) Case Log.  
o Withdrawal log.  

17 | P a g e  
 
• Nurses and physicians who are involved in the date collection 
will be trained in the following areas:  
o Full description of the attended study and the way 
to obtain research consent.  
o Obtaining potassium level from official biochemistry lab result 
o Preparing Intravenous insulin/Dexstrose 50% + Salbutamol Nebulization.  
o Measurement of possible side effected and secondary outcomes.  
During research progress regular visits from the principle investigator will 
be done ensuring the following:  
• Informed Consent forms are properly completed and up to date.  
• Participants are appropriately screened and enrolled.  
• Inclusion and exclusion criteria are applied properly.  
• Randomization procedures are followed, and the blind is maintained.  
• Trial assessments and treatment are conducted in compliance with the protocol. 
• All source documents are attributable, legible, contemporaneous, original, 
accurate, and complete.  
• Medication dosing and documentation are following the protocol.  
• All adverse events and serious adverse events have been documented and 
appropriately reported to the principle Investigator and Institutional 
review board.  
• Reviewing drug accountability records for completeness and accuracy.  
• Checking for protocol deviations/violations that may have occurred.  
• Following up on unresolved issues from previous visits.  
• Providing, or arranging for, additional staff training in problem areas.  
23.  Data handling and record keeping.  
Subject/patient information obtained because of this study is considered 
confidential and disclosure to third parties is prohibited. Medical information 
may be assessed only after approval from the subject/patient to the Investigator. 
The investigator will not disclose any confidential information regarding 
subjects during performance of study duties without justifiable reasons. The 
investigator affirms the subject’s right to protection against invasion of privacy. 
All data collection sheets are collected in a locked and secured box in the 
emergency department and no access is allowed except for investigators. Any 
electronic file containing patient data will be protected by a complicated 
password. No data will be shared though any social platforms including 
WhatsApp. Data can be shared between investigators only by password 
protected Google Drive account. After termination of the study and finishing 
data analysis, data will be stored for a period of 3 year and will be discarded 
safely and securely.   

18 | P a g e  
 
24.  Procedures for reporting deviations from the original plan.  
 Definition of Protocol Violation: A protocol violation refers to any non-compliance 
with the study protocol, procedures, or approved amendments. This can include, but is 
not limited to, enrollment of ineligible participants, missed study visits, incorrect drug 
administration, or failure to obtain informed consent. 
 
 Identification of Violation: All study personnel should be vigilant in identifying 
potential protocol violations. Regular audits and monitoring visits will also serve as a 
mechanism to identify and address violations. 
 
 Immediate Action: Upon identification of a potential protocol violation, immediate 
corrective action should be taken to ensure the safety and rights of the study 
participants. 
 
 Documentation: All protocol violations, regardless of perceived significance, must 
be documented in details. This documentation should include the nature of the 
violation, the date it occurred, the individuals involved, and any corrective actions 
taken. 
 
 Notification: The Principal Investigator (PI) must be informed of all protocol 
violations within 24 hours of discovery. Depending on the severity and nature of the 
violation, the Institutional Review Board (IRB) and the study sponsor may also need 
to be notified. 
 
 Analysis and Reporting: The PI, in collaboration with the study team, will analyze 
the cause of the violation and determine its potential impact on the study's integrity 
and participant safety. A report detailing the violation, its cause, potential impact, and 
corrective actions will be submitted to the IRB and study sponsor as required. 
 
 Preventive Measures: Based on the analysis, preventive measures will be 
implemented to avoid recurrence of similar violations. This may include additional 
training for study personnel, revision of study procedures, or increased monitoring. 
 
 Follow-Up: All protocol violations will be reviewed during regular study team 
meetings to ensure that corrective and preventive actions are effective. Any trends in 
violations will be addressed promptly. 
 
 Transparency: All protocol violations and their resolutions will be transparently 
reported in the study's final publication to ensure the scientific community is aware of 
any potential biases or limitations in the study results. 
 

19 | P a g e  
 
 
Study Protocol Violation Algorithm: 
 
Step 1: Detection 
Monitor study activities regularly. 
Review data collection sheets, informed consent forms, and other study-related documents 
for inconsistencies or missing information. 
 
Step 2: Classification 
Classify the detected issue: Is it a minor deviation or a major violation? 
Refer to the study protocol for definitions and examples. 
 
Step 3: Immediate Action 
For minor deviations: Correct the issue immediately, e.g., obtain a missing signature on a 
consent form. 
For major violations: Pause the affected study activity and ensure the safety of the 
participant. 
 
Step 4: Documentation 
Record the violation in the "Subject Deviation/Unanticipated Problem Case Log." 
Include details such as the nature of the violation, date, individuals involved, and corrective 
actions taken. 
 
Step 5: Notification 
Inform the Principal Investigator (PI) within 24 hours of discovery. 
If severe, notify the Institutional Review Board (IRB) within 14 working days. 
 
Step 6: Analysis 
The PI and study team analyze the cause and potential impact of the violation. 
Determine if the violation affects participant safety, data integrity, or participant willingness 
to continue. 
 
Step 7: Report Compilation 
Compile a detailed report of the violation, its cause, potential impact, and corrective actions. 
Submit the report to the IRB and any other relevant bodies. 
 
Step 8: Preventive Measures 
Implement measures to prevent recurrence based on the analysis. 
This could include additional training, revision of study procedures, or increased monitoring. 
 
Step 9: Follow-Up 
Review all protocol violations in regular study team meetings. 
Address any trends or repeated violations promptly. 
 
Step 10: Transparency & Publication 
Ensure all protocol violations and resolutions are transparently reported in the study's final 
publication. 
 

20 | P a g e  
 
Anticipated Protocol Violations: 
 
Informed Consent Issues: 
1. Missing original signed and dated consent form. 
2. Use of an incorrect version of the informed consent form. 
3. Missing pages from the executed consent form. 
4. Inappropriate documentation of consent, such as missing signatures or the individual 
obtaining consent not being listed on the IRB approved application. 
Timing Issues: 
1. The subject/patient falls outside of the window of time indicated by the protocol. 
 
Recruitment and Enrollment: 
2. Implementation of unapproved recruitment procedures. 
3. Enrollment of participants who do not meet the inclusion and exclusion criteria. 
 
Treatment and Assessment: 
1. Incorrect drug administration or dosage. 
2. Failure to maintain the study's blind. 
3. Not following randomization procedures. 
4. Trial assessments not conducted in compliance with the protocol. 
 
Documentation and Data Handling: 
1. Inaccurate or incomplete source documents. 
2. Medication dosing and documentation not following the protocol. 
3. Adverse events not being documented or reported to the PI and IRB. 
25.  Anticipated results   
The antihyperkalemic measure effect of intravenous regular insulin 5units is not inferior to 
intravenous regular insulin 10 units and there will be fewer side effects.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

21 | P a g e  
 
 
 
 
 
 
 
 
 
 
26. References: 
1. Ron M. Walls, MD. Hyperkalemia. Rosen emergency medince Concepts and Clinical 
practice. 9th. Philadelphia : Elsevier, 2018, 117, pp. 1516 - 1519. 
2. Judith E. Tintinalli, MD, MS. Hyperkalemia. Tintinalli’s Emergency Medicine a 
comprehensive study guide. 9th. s.l. : McGraw-Hill Education, 2020, 17, p. 89. 
3. David B Mount, MD. Causes and evaluation of hyperkalemia in adults. Uptodate. 
[Online] May 26, 2020. [Cited: October 29, 2021.] 
https://www.uptodate.com/contents/causes-and-evaluation-of-hyperkalemia-in-
adults?search=hyperkalemia&source=search_result&selectedTitle=2~150&usage_type=defa
ult&display_rank=2. 
4. —. Treatment and prevention of hyperkalemia in adults. Uptodate. [Online] October 29, 
2021. [Cited: October 30, 2021.] https://www.uptodate.com/contents/treatment-and-
prevention-of-hyperkalemia-in-adults. 
5. Eleanor Lederer, MD, FASN. Hyperkalemia Treatment & Management. Medscape. 
[Online] [Cited: October 30, 2021.] https://emedicine.medscape.com/article/240903-
treatment#d8. 
6. A comparison of insulin doses for treatment of hyperkalaemia in intensive care unit 
patients with renal insufficiency. Miranda Verdier PharmD, Joshua M.DeMott PharmD, 
MSc, Gary D.PeksaPharmD, MBA. 6, s.l. : ELSEVIER, June 21, 2021, Australian Critical 
Care, Vol. 34. 
7. Treatment of Hyperkalemia With a Low-Dose Insulin Protocol Is Effective and Results in 
Reduced Hypoglycemia. Bairbre A. McNicholas, Mai H. Pham, Katrina Carli, Chang 
Huei Chen, Nancy Colobong-Smith, Arthur Eric Anderson and Hien Pham. october 23, 
2017, KI reports, pp. 328–336. 
https://www.researchgate.net/publication/320590998_Treatment_of_Hyperkalemia_With_a_
Low-Dose_Insulin_Protocol_Is_Effective_and_Results_in_Reduced_Hypoglycemia. 
8. Comparison of IV Insulin Dosing Strategies for. Kayvan Moussavi, PharmD, BCCCP, et 
al., et al. s.l. : Wolters Kluwer Health, Inc, 2020, Critical Care Explorations Jaurnal, Vol. 2. 
9. A Comparison of Insulin Doses for the Treatment of Hyperkalemia in Patients with Renal 
Insufficiency. Heather A. LaRue, Gary Daniel Peksa, Shital C. Shah. 12, December 2017, 
American college of clinical pharmacy, Vol. 37, pp. 1516-1522. 
10. Reduced alternative insulin dosing in hyperkalemia: A meta-analysis of effects on 
hypoglycemia and potassium reduction. Kayvan Moussavi, Joshua Garcia, Eglis Tellez-
Corrales, Scott Fitter. 7, s.l. : American College of Clinical Pharmacy, May 16, 2021, Vol. 
41, pp. 598-607. https://accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.2596. 
11. Optimal Dose and Method of Administration of Intravenous Insulin in the Management of 
Emergency Hyperkalemia: A Systematic Review. Ziv Harel, Kamel S. Kamel. [ed.] Sao 

22 | P a g e  
 
Paulo State University, BRAZIL Pasqual Barretti. may 5, 2016, PLOS ONE. 
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0154963. 
12. Adrian Vella, MD. Hypoglycemia in adults without diabetes mellitus: Diagnostic 
approach. Up-To-Date. [Online] July 23, 2020. [Cited: December 31, 2022.] 
https://www.uptodate.com/contents/hypoglycemia-in-adults-without-diabetes-mellitus-
diagnostic-
approach?search=hypoglycemia%20&source=search_result&selectedTitle=1~150&usage_ty
pe=default&display_rank=1. 
13. ames Neuenschwander, MD, FACEP (co-chair) Matthew Weir, MD (co-chair) Terra 
Armstead DNP, RN, CEN Jason J. Bischof, MD Joanna Hudson, PharmD W. Frank 
Peacock, MD, FACC, FESC, FACEP Zubaid Rafique, MD, FACEP. Hyper K recognition 
and treatment of Hyperkalemia in the ED. American College of Emergency Physicians. 
[Online] 05 08, 2022. [Cited: 08 05, 2022.] https://www.acep.org/patient-care/hyperk/. 
14. Reduced Versus Conventional Dose Insulin for hyperkalemia Treatment. Joshua Garcia, 
PharmD, BCPS1,2, Megan Pintens, PharmD, BCPS, BCCCP2, Amanda Morris, 
PharmD, BCPS, BCCCP2, Paul Takamoto, PharmD2, Laura Baumgartner, PharmD, 
BCPS, BCCCP2,3, Chelsea L. Tasaka, PharmD, BCPS, BCCCP2,4. 3, 2020, Journal of 
Pharmacy practice, Vol. 33, pp. 262 - 266. 
15. Baig, Dr Tom Pickett & Israr. Treatment guideline : Hyperkalemia. NHS 
Gloucestershire Hospitals. [Online] NHS, February 2021. [Cited: 10 26, 2022.] 
https://www.gloshospitals.nhs.uk/gps/treatment-guidelines/hyperkalaemia/. 
16. Comparison of IV Insulin Dosing Strategies for Hyperkalemia in the Emergency 
Department. Kayvan Moussavi, PharmD, BCCCP, et al., et al. s.l. : Wolters Kluwer 
Health, Inc, 2020, Critical Care Explorations Jaurnal, Vol. 2. 
 
 
 
 
 

23 | P a g e  
 
27. Appendix: 
Data collection sheet  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics
Hospital
Location (ED/Inpation)
Gender
Age
DM type
HTN
IHD
ESRD
Last Dialysis session (if any)
Other comorbidities
Home Medications
Suspected cause of Hyperkalemia
CBC
Hb:
WBC:
Plat:
UE
AG:
HCO3:
Creat:
GFR:
Na:
K:
Mg serum
Follow up /time line (minutes)
0
60
120
Potassium
Blood sugar
Total amount of Intravenous fluid received during the study period / type of IV fluid
Other medications adminestered
Urine output (if any)
Needed another antihyperkalemic messures?
Needed Urgent/Emergent Dialysis?
Patient hospital ID
Study Code:

24 | P a g e  
 
Written informed consent 
 
5 versus 10 units of insulin in hyperkalemia management: Double Blinded, Randomized 
Clinical Trial 
5/10 trial 
Introduction: 
We are researchers from Oman medical speciality board (OMSB) conducting a research on 
the efficacy and safety of different insulin doses (5 units versus 10 units of regular insulin) in 
management of hyperkalemia. Hyperkalemia is the most common electrolytes imbalance, and 
it has significant side effects on the heart. This consent will include all the information about 
our study and the protocol in addition to the rationale of our study. 
 
The aim of the study 
Hyperkalemia is a life threatening electrolyte imbalance and needs immediate management. 
Different medications are used to treat hyperkalemia. One of these medications is insulin.  
Different doses of insulin are used in treating hyperkalemia depending on the physician's 
judgment and patient condition. No previous prospective study done to compare the doses of 
insulin in hyperkalemia. Insulin is associated with hypoglycemia as a side effect especially 
with high doses. Our investigators will allocate you into one of two groups of doses ( 5 units 
vs 10 units) of insulin and will follow the effect on reducing potassium level, in addition 
following up blood sugar level. At the same time. At the same time, You also will receive 
dextrose IV to prevent you from hypoglycemia. 
 
Type research intervention: 
Comparing between two doses of insulin in lowering hyperkalemia. 
 
Participant collection: 
All patients above 18 years, whom having hyperkalemia will be evaluated to participate in 
the study. 
 
Voluntary participation: 
Your participation in this research is entirely voluntary. It is your choice whether to 
participate or not. All the services you receive at this hospital will continue and nothing will 
change If you choose not to participate in this research project, you will be offered the same 
treatment but without registering your data, as it is the same treatment offered in this hospital 
for hyperkalemia. You may change your mind later and stop participating even if you agreed 
earlier. 
  
Information about the study 
This study will start after identifying hyperkalemia, and the treating physician identifies you 
as a candidate for the treatment. You will be randomised in 2 different groups of insulin 
doses, and will be followed and monitored throughout the entire study period.  All other 
antihyperkalemic medications will be started the same with no change from the routine 
treatment. At the same time, You also will receive dextrose IV to prevent you from 
hypoglycemia. 
. 
 
 
 

25 | P a g e  
 
Study Procedure: 
Because till now no prospective study has been done to compare the 2 doses of insulin in 
lowering hyperkalemia, and the increase of risk of hypoglycemia with the high dose of 
insulin. This study aims to select the proper and the safest dose for our patients. 
The patient will follow the routine path of clinical evaluation and management. If a patient is 
found to have hyperkalemia more than or equal 5.5 mEq/L he/she will be screened for 
inclusion and exclusion criteria. The patient or the family member who can give consent for 
the patient will be informed about the study. After explaining all the details for the 
patients/relative a written consent will be taken with an Arabic and English copy will be 
provided for further details.  
Once consent is signed a physician will randomise the patient into one of the two different 
groups of insulin doses. One group will receive 5 units of insulin regular and the second 
group will receive 10 units of insulin regular. At the same time, You also will receive 
dextrose IV to prevent you from hypoglycemia. 
. The group selection will be randomised before the start of the study, and the physician will 
not decide which patient will join which group to maintain good randomization and to have 
proper results from the study. Serial labs will be collected at different time intervals to 
monitor the patient and his response. Labs will be collected at 0, 120 minutes to trace 
potassium level. Blood sugar will be monitored by Glucometer at 0, 60, 120 minutes or as 
indicated by the treating physician according to your symptoms. Patients will receive all 
treatments for hyperkalemia without change from the hospital followed protocol except for 
the dose of insulin. If there is any concern at any point during the study feel free to contact 
me or to contact the treating physician for any clarification. If there is any concern regarding 
your safety during the study you can stop at any time and the local protocol/guidelines will be 
followed for your management. 
 
Risk: 
Risk of hypoglycemia as a side effect of higher insulin dose, but it is managed by the sugar 
that is given with insulin at the start of the study. All side effects will be monitored as per the 
protocol, and medications side effects will be traced, and will be treated as soon as possible 
once identified. 
 
Benefit 
This will help us to clarify the proper dose of insulin in treating hyperkalemia with the least 
side effect to patients. Your participation will improve the next patient care once the data 
analyses. 
 
Reimbursements  
You will not be given any other money or gifts to take part in this research.  
 
Confidentiality  
The information that collected by our investigators from this research project will be kept 
confidential. Information about you that will be collected during the research will be put 
away and no-one but the researchers/investigators will be able to see it. Any information 
about you will have a number on it instead of your name. Only the researchers/investigators 
will know what your number is, and the information will be lock up with a lock and key.  
 
Sharing the Results  
The knowledge that our investigators get from doing this research will be shared with you 
through community meetings before it is made widely available to the public. Confidential 

26 | P a g e  
 
information will not be shared. There will be small meetings in the community, and these will 
be announced. After these meetings, our research team will publish the results in order that 
other interested people may learn from our research.  
 
Right to Refuse or Withdraw  
You do not have to take part in this research if you do not wish to do so and refusing to 
participate will not affect your treatment at this emergency department in any way. You will 
still have all the benefits and you may stop participating in the research at any time that you 
wish without losing any of your rights as a patient here. Your treatment at this hospital will 
not be affected in any way.  
 
Alternatives to Participating  
If you do not wish to take part in the research, you will be provided with the established 
standard treatment available at the hospital.  
 
Contact information  
 
I have read the foregoing information, or it has been read to me. I have had the opportunity to 
ask questions about it. Any questions that I asked, they have been answered to my 
satisfaction. I consent voluntarily to participate as a participant in this research.   
Authorised to consent 
name 
Relationship to the patient  Signature  
Date 
 
 
 
 
 
Researcher/Doctor: 
Signature: 
Date: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

27 | P a g e  
 
Withdrawal form 
Subject ID:                                                            Date:            /             / 
                                                                                          Month                  Day                  Year 
Withdrawal form 
Date subject went Off Study:                     /                     /  
                                                      Month                Day 
 
Year 
INDICATE OFF STUDY REASON: (select only one)  
       Study Activities Completed 
If the subject was withdrawn prior to completing the study (i.e. early withdrawal), select one of 
the following:  
             Subject withdrawn – by Subject PRIOR to enrollment**  
             Subject withdrawn – by Subject AFTER enrollment**  
             Subject withdrawn – by PI PRIOR to enrollment**  
             Subject withdrawn – by PI AFTER enrollment** 
             Death  
             Other** 
 
If the subject was withdrawn, indicate specific reason(s): (select all that apply)  
                               Subject lost to follow-up  
                               Subject refused follow-up  
                               Due to adverse events or complications  
                               Other… 
**Additional explanation required: 
 
 
 
Form Completed by:  

28 | P a g e  
 
Medications administration form: 
 
 
 
 
 
 
======================================================= 
 
 
 
 
 
 
 
 

29 | P a g e  
 
Study Flow chart: 
 
 
 
 
 
 
 
 
                     ↓ 
 
 
 
 
 
     
                                                                              ↓ 
 
 
 
           
                                           ↙ 
 
                   ↘ 
 
 
                                                              ↘                                                               ↙ 
 
 
 
 
 
 
                                           ↓ 
 
     STUDY FLOW 
CHART 
Attending physician 
1.
Patient will receive Salbutamol nebulization 10 mg in 3ml normal saline over 15 minutes. 
2.
((The physician will decide the need of cardiac stabilizing agents (e.g Calcium Gluconate) as indicated by the 
physician in-charge of the patient.)) 
3.
Will screen inclusion and exclusion criteria. 
4.
Explain all study procedure to the patient. 
5.
Obtain informed consent with signature. 
Randomization 
1. Open study envelope. 
2. Take the included code in that envelope and stick it to the patient data collection 
sheet. 
3. Give medication instructions card to the nurse in-charge of the patient  
4
P
ib i
li R
l
i
h
10
i
i
i
h
(i
li
5 IU of Insulin 
10 IU of Insulin 
Assessment 
Potassium level: 0 and 120 minutes. 
Blood sugar: 0, 60 and 120 minutes.  
Report any adverse event 
 
Termination 
The study will be over at 120 min from 
medication administration 
Patient diagnosed in the ED with hyperkalemia, K ≥ 5,5 mEq/l from official Laboratory test, will 
Start all antihyperkalemic measures, Ca gluconate need will be decided by the treating physician . 
Patient in whom K level was checked from VBG and found to be ≥ 5.5 mEq/l 
They will go through the same process. 
If the official lab K level result below 5.5mEq/l, or hemolyzed patient will be excluded from the study. 
 

30 | P a g e  
 
Disposition 
Hypoglycemia, RBS ≤ 3.89 
mmol/l  in DM patient or 
RBS ≤ 3 mmol/l in nonDM 
patient 
Alert 
Yes                                          no 
Hypoglycemia management flow chart 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Consider discharge after 4h uneventful observation if,  

Hypoglycemia fully and rapidly reversed without continuous infusion of 
dextrose 

Tolerated a full meal in ED 

Clear and innocuous cause identified with recurrence unlikely 

Adequate patient understanding, home support/monitoring, and ability to 
detect/prevent recurrence with close primary care follow-up 
Oral glucose 
E.g.: Sandwich 
or juice, etc... 
IV access 
Dextrose 50% 50ml 
No IV access 
Glucagon 1mg 
IM,SC 
Check serum glucose q 30min ×4h, repeating 
management algorithm as needed. 
Consider Dextrose continues infusion after 2 
cycles. 
Monitoring 

31 | P a g e  
 
Ministry of Health hyperkalemia management: 
 
 

32 | P a g e  
 
 
 
 
 
 
 
 
 
 
 
 
 

33 | P a g e  
 
 
 
Serious Adverse Event Case Log 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

34 | P a g e  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject Deviation/Unanticipated Problem Case Log