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

Phase 4

Recruiting

Conditions: Hyperkalemia

Registration Number: 2024-514889-40-00

Lead Sponsor: Centre Hospitalier Universitaire De Nantes

Brief Summary: 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.

Detailed Description: InSaKa trial is a therapeutic, controlled, open label, with parallel groups of treatment in a 1:1:1 ratio, multi-centre, national and randomized clinical trial to compare insulin/dextrose intravenous infusion, nebulized salbutamol or combination of salbutamol and insulin/dextrose to reduce serum potassium levels at 60 minutes. Eligible patients will be recruited in the emergency department and included in the study after testing for inclusion and non-inclusion criteria. Patients will be eligible for the randomization if they had a serum potassium concentration superior or equal to 6 mmol per liter. Randomization, which will be performed centrally, will be stratified 1) according to the serum potassium level at baseline of the initial treatment phase (6 to \< 6.5 mmol per liter \[moderate hyperkalemia\] AND superior or equal to 6.5 mmol per liter \[severe hyperkalemia\]), and 2) according to the prescription or not of intravenous diuretics during the 6 previous hours. The protocol will be approved by the ethical committee (random allocation) of the IRB. All patients will provide written informed consent and the study will be performed in accordance with the International Conference on Harmonization Guidelines for Good Clinical Practice. All electrocardiograms will be read at a core electrocardiographic laboratory. At the time of screening, patients who meet all the inclusion and do not have non-inclusion criteria will be assigned to one of the 3 groups of treatment. The serum potassium will be then measured at 60 minutes. If the patient still has hyperkalemia at 60 minutes, the patient will be re-administered a treatment, left at the discretion of the physician in charge. This treatment might include insulin/dextrose intravenous infusion, nebulized salbutamol, the combination of nebulized salbutamol and insulin/dextrose intravenous infusion, bicarbonate, diuretics or dialysis. Especially, bicarbonate should be prescribed in case of metabolic acidosis or hypovolemic shock, and diuretics in case of acute heart failure. Importantly, if the patient has a major cardiovascular event before 60 minutes, all these treatments might be prescribed at the discretion of the physician in charge, if the clinical situation requires one or more of these therapeutic options, and based on up-to-date clinical practice guidelines and recommendations. Serum potassium levels will be measured at local laboratories at baseline and 60, 180 minutes and 24 hours. They will perform a visual inspection and a validated semi-quantitative test on each blood sample as an assessment for hemolysis. An independent adjudication committee will adjudicate all major cardiovascular events. The trial will be monitored by a Data Safety Monitoring Board.

Recruitment & Eligibility

Status: Ongoing, recruiting

Sex: Not specified

Target Recruitment: 525

Inclusion Criteria

Patient older than 18-year old

Patient admitted to the emergency department

Local laboratory serum potassium level superior or equal to 5,5 mmol/l

Patient who provide written informed consent prior to participation in the study

Exclusion Criteria

Hemolysis of blood samples or thrombocytosis > 106/mm3 or hyperleukocytosis > 105/mm3 on the first blood sample suspecting a pseudohyperkalemia

Acute coronary syndrome

Patient not affiliated to a health insurance plan

Patient under guardianship, curatorship or safeguard of justice

Acute complications of diabetes: diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome

Pregnant or lactating woman, women with childbearing potential who didn’t have effective contraception.

Patient expected to require emergency intubation and ventilation

Patient expected to require dialysis within the first 60 minutes

Patient expected to require diuretics within the first 60 minutes

Patient expected to require bicarbonate within the first 60 minutes

Patient with heart rhythm disorders or high grade atrioventricular bloc that require urgent medication as soon as admission or serum potassium level result

Hypersensitivity to the tested active substance or to the excipients of salbutamol or insulin treatment

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Mean change in the absolute serum potassium level from baseline to 60 minutes (measured in mmol/l)		Mean change in the absolute serum potassium level from baseline to 60 minutes (measured in mmol/l)

Secondary Outcome Measures

Name	Time	Method
Proportion of major cardiovascular events at 60, 180 minutes and 24 hours		Proportion of major cardiovascular events at 60, 180 minutes and 24 hours
Mean change in the serum potassium level from baseline to 180 minutes and 24 hours		Mean change in the serum potassium level from baseline to 180 minutes and 24 hours
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		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
Proportion of patients who require re-treatment or dialysis at 60, 180 minutes and 24 hours		Proportion of patients who require re-treatment or dialysis at 60, 180 minutes and 24 hours
Proportion of patients with adverse effects at 60 and 180 minutes		Proportion of patients with adverse effects at 60 and 180 minutes
Proportion of patients with heart rhythm disorders or high grade atrioventricular bloc that required urgent medication during the first 180 minutes		Proportion of patients with heart rhythm disorders or high grade atrioventricular bloc that required urgent medication during the first 180 minutes
Proportion of patients with electrocardiographic abnormalities, at 60, 180 minutes and 24 hours		Proportion of patients with electrocardiographic abnormalities, at 60, 180 minutes and 24 hours

Trial Locations

Locations (13): Centre Hospitalier Universitaire De Nice
🇫🇷
Nice, France
Assistance Publique Hopitaux De Paris
🇫🇷
Colombes Cedex, France
Centre Hospitalier Universitaire De Poitiers
🇫🇷
Poitiers, France
University Hospital Of Clermont-Ferrand
🇫🇷
Clermont Ferrand Cedex 1, France
Les Hopitaux Universitaires De Strasbourg
🇫🇷
Strasbourg Cedex 2, France
Hopital Saint Antoine
🇫🇷
Paris Cedex 12, France
CHRU De Nancy
🇫🇷
Nancy, France
Centre Hospitalier Universitaire D'Angers
🇫🇷
Angers, France
Centre Hospitalier Universitaire De Nantes
🇫🇷
Nantes, France
Centre Hospitalier d'Agen
🇫🇷
Agen, France
Scroll for more (3 remaining)
Centre Hospitalier Universitaire De Nice
🇫🇷Nice, France
LEVRAUT Jacques
Site contact
+33492033335
levraut.j@chu-nice.fr