Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000617460
Ethics application status
Approved
Date submitted
30/05/2025
Date registered
13/06/2025
Date last updated
13/06/2025
Date data sharing statement initially provided
13/06/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Insulin-dextrose vs glucose-only therapy for the treatment of hyperkalaemia
Scientific title
Hypertonic Glucose vs Insulin-dextrose to Prevent HypoGlycaemia following treatment for HyperKalaemia (HIGH K): A randomised controlled trial in adult participants
Secondary ID [1] 314561 0
Nil known
Universal Trial Number (UTN)
Trial acronym
HIGHK
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hyperkalaemia 337663 0
Hypoglycaemia 337664 0
Condition category
Condition code
Emergency medicine 333994 333994 0 0
Other emergency care
Metabolic and Endocrine 334058 334058 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Glucose-Only Therapy:
10mL (2.2mmol) calcium gluconate intravenously over 2-3 minutes
10mg salbutamol via nebulisation
100 mL (50%) dextrose administered intravenously over 10 minutes, followed by 250 mL (10%) dextrose administered intravenously over 2 hours.

Interventions will be administered by a registered nurse. Staff will be educated on the trial protocol before the first patient is enrolled. Adherence to protocol will be assessed through retrospective chart review.
Intervention code [1] 331184 0
Treatment: Drugs
Comparator / control treatment
Insulin-Dextrose Therapy (IDT):
10mL (2.2mmol) calcium gluconate intravenously over 2-3 minutes
10mg salbutamol via nebulisation
10 units intravenous human insulin (Actrapid) with 50 mL (50%) dextrose administered over 10 minutes, followed by 250mL (0.9%) sodium chloride

Interventions will be administered by a registered nurse. Staff will be educated on the trial protocol before the first patient is enrolled. Adherence to protocol will be assessed through retrospective chart review.
Control group
Active

Outcomes
Primary outcome [1] 341656 0
Incidence of hypoglycaemia defined as blood glucose <3.9 mmol/L.
Timepoint [1] 341656 0
At basline and then hourly for 6 hours post commencement of treatment.
Primary outcome [2] 341657 0
Mean change in serum potassium from baseline.
Timepoint [2] 341657 0
At basline and then at 1 hour, 2 hours (primary timepoint) and 6 hours post commencement of treatment.
Secondary outcome [1] 448225 0
Hypoglycaemia severity
Timepoint [1] 448225 0
At basline and then hourly for 6 hours post commencement of treatment.
Secondary outcome [2] 448226 0
Proportion of participants requiring rescue insulin therapy (insulin administered outside the protocol due to inadequate potassium response (clinician discretion) or due to clinical deterioration).
Timepoint [2] 448226 0
Recorded anytime the rescue occurs (within the study period of 6 hours) and assessed at the conclusion of the study intervention period.
Secondary outcome [3] 448227 0
Proportion of participants achieving a clinically significant potassium reduction (defined as greater than or equal to -0.5 mmol/L from baseline).
Timepoint [3] 448227 0
All patients will have a serum potassium value taken at 2 hours post treatment commencement. The proportion of patients achieving this endpoint will then be assessed at the conclusion of the study intervention period.
Secondary outcome [4] 448228 0
Presence of hyperkalaemic ECG changes at baseline
Timepoint [4] 448228 0
The baseline ECG (taken upon presentation to the Emergency Department before any hyperkalaemia treatment options are administered)
Secondary outcome [5] 448229 0
Insulin levels (mU/L): NB: assay detects both exogenous and endogenous insulin.
Timepoint [5] 448229 0
Measured at baseline, 1 hour, and 2 hours post commencement of treatment.
Secondary outcome [6] 448509 0
Resolution of ECG changes
Timepoint [6] 448509 0
Resolution of baseline ECG changes will be assessed by comparing the baseline ECG data to the ECG taken at 1 hour, 2 hours, and 4-6 hours post treatment.

Eligibility
Key inclusion criteria
Adults (18 years or older), hyperkalaemia (serum or blood gas potassium >5.5 mmol/L), treating ED clinician determines that treatment for hyperkalaemia is necessary and agrees to randomize the patient to one of the treatment arms, ability to provide informed consent or, if the patient lacks capacity, consent obtained from a legally authorised substitute decision-maker.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Diabetes mellitus, pre-treatment blood glucose >7.8 mmol/L, requiring resuscitation, intravenous insulin administered before randomisation, suspected or confirmed intracranial/ intraspinal ischaemic or haemorrhagic stroke, known glucose-galactose malabsorption syndrome, known allergy to corn (maize) and corn products.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Randomisation to be fascilitated through RedCap randomisation module (randomisation table uploaded into RedCap database).
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Stratified, block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis
A total sample size of 95 participants (approx. 48 per group) was determined to provide 80% power to detect a difference in hypoglycaemia incidence between treatment arms (expected: 17% for insulin–dextrose therapy, 0% for glucose-only), with a=0.05 and up to 10% attrition. A design effect of 1.1 was applied to account for possible repeat enrolments (ICC=0.3, average 1.2 enrolments per participant). This sample size also supports evaluation of non-inferiority for potassium reduction at 2 hours (non-inferiority margin: –0.5 mmol/L; SD: 0.8 mmol/L).

Primary safety (hypoglycaemia incidence) will be compared using Fisher’s exact test; if repeat enrolments introduce clustering, a generalised linear model will be used. For the primary efficacy outcome (potassium change), group means and differences will be reported with 95% confidence intervals, and non-inferiority assessed. Analyses follow a modified intention-to-treat approach. Secondary outcomes will use descriptive statistics and, where applicable, linear mixed-effects models. Missing data will be excluded if minimal (<5%) or handled via mixed modelling. Statistical significance is defined as p<0.05.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/02/2026
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
95
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 27986 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 44183 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 319109 0
Hospital
Name [1] 319109 0
The Royal Brisbane and Women's Hospital
Country [1] 319109 0
Australia
Primary sponsor type
University
Name
University of Queensland
Address
Country
Australia
Secondary sponsor category [1] 321618 0
None
Name [1] 321618 0
Address [1] 321618 0
Country [1] 321618 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317706 0
Metro North Health Human Research Ethics Committee
Ethics committee address [1] 317706 0
Ethics committee country [1] 317706 0
Australia
Date submitted for ethics approval [1] 317706 0
20/01/2025
Approval date [1] 317706 0
27/05/2025
Ethics approval number [1] 317706 0
HREC/2025/MNH/115385

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 141878 0
Dr Julian Williams
Address 141878 0
Royal Brisbane and Women's Hospital, Emergency and Trauma Centre, Butterfield St, Herston, 4029, QLD
Country 141878 0
Australia
Phone 141878 0
+61 417625653
Fax 141878 0
Email 141878 0
[email protected]
Contact person for public queries
Name 141879 0
Samuel Ford
Address 141879 0
Royal Brisbane and Women's Hospital, Emergency and Trauma Centre, Butterfield St, Herston, 4029, QLD
Country 141879 0
Australia
Phone 141879 0
+61 499191700
Fax 141879 0
Email 141879 0
[email protected]
Contact person for scientific queries
Name 141880 0
Samuel Ford
Address 141880 0
Royal Brisbane and Women's Hospital, Emergency and Trauma Centre, Butterfield St, Herston, 4029, QLD
Country 141880 0
Australia
Phone 141880 0
+61 499191700
Fax 141880 0
Email 141880 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Study protocol    HIGHK Protocol 250430 v2 Clean.docx
Ethical approval    115385 HREC Approval Ltr 27.05.2025 Amended 30.05.25.pdf


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.