Insulin Dextrose Infusion vs Nebulized Salbutamol vs Combination of Salbutamol and Insulin Dextrose in Acute Hyperkalemia
Insulin Dextrose Infusion vs Nebulized Salbutamol vs Combination of Salbutamol and Insulin Dextrose in Acute Hyperkalemia
Hyperkalemia is a common electrolyte disorder, especially among patients with chronic kidney
 disease, diabetes mellitus, or heart failure. Globally, the reported incidence of
 hyperkalemia varies from 1.1 to 10 per 100 hospitalizations, depending on the patient cohort
 and comorbidities. Hyperkalemia is a potentially life-threatening electrolyte disturbance
 that can be fatal if left untreated. Several studies have established the association between
 hyperkalemia and all-cause mortality. Because of the deleterious cardiac effects of
 hyperkalemia, its management is an emergency intervention. However, robust evidence is
 lacking to guide the emergency management of patients with hyperkalemia. Emergency treatment
 approaches are largely based on small studies, anecdotal experience, and traditionally
 accepted practice patterns within institutions. Therefore, a rigorous evaluation of the
 first-line treatments of hyperkalemia in emergency departments is needed and a large scale
 randomized clinical trial is warranted before robust recommendations for clinical practice
 can be made. Our clinical trial will improve the safety of patients with acute hyperkalemia
 and will help clinicians in their day by day practice to choose the treatment that
 significantly reduces morbidity and mortality during acute hyperkalemia management. Our
 results will be delivered in a timely fashion, owing to the high prevalence of hyperkalemia
 in the emergency department setting and to the commitment of the INI-CRCT network of
 Excellence, along with ED specialists used to work jointly.

 the primary objective of our trial is 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.
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.
Inclusion Criteria:

 -  Patient older than 18 years old

 -  Patient admitted to the emergency department,

 -  Patient with local laboratory serum potassium level superior or equal to 6 mmol/l,

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

 Exclusion Criteria:

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

 -  Diabetic ketoacidosis or 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, diuretics or bicarbonate within the first 60
 minutes,

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

 -  Hypersensitivity to the tested active substance or excipients,

 -  Acute coronary syndrome,

 -  Patient not affiliated to a health insurance plan,

 -  Patient under guardianship, curatorship or safeguard of justice.

 -  The contraceptives considered as highly effective and acceptable by CTFG
 recommendations will be considered effective under this protocol. The list of
 contraceptives considered as highly effective and acceptable by CTFG
 recommendations is detailed in Appendix 7