InSaKa trial: Insulin dextrose infusion versus nebulized salbutamol versus combination of salbutamol and insulin dextrose in acute hyperkalemia: a randomized clinical trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nantes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

20 Dec 2019 → 20 Dec 2025

Decision date (initial)

2024-07-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514889-40-00

EudraCT number

2019-002710-39

ClinicalTrials.gov

NCT04012138

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

to compare insulin/dextrose intravenous infusion, nebulized salbutamol or combination of nebulized salbutamol and insulin/dextrose intravenous infusion to reduce serum potassium concentration at 60 minutes, as first-line treatment, in emergency departments.

Secondary objectives 7

1. Compare the 3 groups of treatment for reducing serum potassium concentration at 180 minutes and 24 hours.
2. Compare the proportion of patients with normokalemia (from 4 to 4.9 mmol/l) at 60, 180 minutes and 24 hours
3. Compare the proportion of patients who require re-treatment or dialysis at 60, 180 minutes and 24 hours
4. Compare selected adverse effects at 60 and 180 minutes: Hypokalemia (<3.5 mmol/l or < 4 mmol/l), Hypomagnesemia (< 0.58 mmol/l), Hypoglycemia (< 4.0 mmol/l), Hyperglycemia (> 10.0 mmol/l), Gastrointestinal disorders, Tachycardia (> 130/min), Tremor
5. Compare, on a standard 12-lead electrocardiogram, the proportion of patients with heart rhythm disorders or high grade atrioventricular bloc, that required urgent medication during the first 180 minutes
6. Compare other ECG abnormalities at 60, 180 minutes and 24 hours: Auricular extrasystoles, Ventricular extrasystoles, Atrioventricular block (other grade), QRS Interval Prolongation, QTc interval prolongation
7. Compare the rates of major cardiovascular events at 60, 180 minutes and 24 hours: cardiac arrest, stroke, acute heart failure, complete atrioventricular block with ventricular rate under 30 bpm, ventricular fibrillation, ventricular tachycardia

Conditions and MedDRA coding

Hyperkalemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Patient older than 18-year old
2. Patient admitted to the emergency department
3. Local laboratory serum potassium level superior or equal to 5,5 mmol/l
4. Patient who provide written informed consent prior to participation in the study

Exclusion criteria 12

1. Hemolysis of blood samples or thrombocytosis > 106/mm3 or hyperleukocytosis > 105/mm3 on the first blood sample suspecting a pseudohyperkalemia
2. Acute complications of diabetes: diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome
3. Pregnant or lactating woman, women with childbearing potential who didn’t have effective contraception.
4. Patient expected to require emergency intubation and ventilation
5. Patient expected to require dialysis within the first 60 minutes
6. Patient expected to require diuretics within the first 60 minutes
7. Patient expected to require bicarbonate within the first 60 minutes
8. Patient with heart rhythm disorders or high grade atrioventricular bloc that require urgent medication as soon as admission or serum potassium level result
9. Hypersensitivity to the tested active substance or to the excipients of salbutamol or insulin treatment
10. Acute coronary syndrome
11. Patient not affiliated to a health insurance plan
12. Patient under guardianship, curatorship or safeguard of justice

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean change in the absolute serum potassium level from baseline to 60 minutes (measured in mmol/l)

Secondary endpoints 7

1. Mean change in the serum potassium level from baseline to 180 minutes and 24 hours
2. Proportion of patients who had a serum potassium level of 4 mmol/l to less than 4.9 mmol/l at 60, 180 minutes and 24 hours
3. Proportion of patients who require re-treatment or dialysis at 60, 180 minutes and 24 hours
4. Proportion of patients with adverse effects at 60 and 180 minutes
5. Proportion of patients with heart rhythm disorders or high grade atrioventricular bloc that required urgent medication during the first 180 minutes
6. Proportion of patients with electrocardiographic abnormalities, at 60, 180 minutes and 24 hours
7. Proportion of major cardiovascular events at 60, 180 minutes and 24 hours

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nantes

Sponsor organisation

Centre Hospitalier Universitaire De Nantes

Address

5 Allee De L Ile Gloriette, Cs 69301 Cs 69301

City

Nantes Cedex 1

Postcode

44093

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Emmanuel MONTASSIER

Public contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Emmanuel MONTASSIER

Locations

1 EU/EEA country · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications