Insulin Dextrose Infusion vs Nebulized Salbutamol vs Combination of Salbutamol and Insulin Dextrose in Acute Hyperkalemia

NCT ID: NCT04012138

Last Updated: 2024-04-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 525 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-20
• Study Completion Date: 2026-06-20

Brief Summary

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.

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.

Conditions

Hyperkalemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Salbutamol

Patients in this experimental group will receive : 10 mg of salbutamol nebulized in 30 minutes (with oxygen 8 liters per minute or with air);

Group Type: EXPERIMENTAL

Salbutamol

Intervention Type: DRUG

10 mg of salbutamol nebulized in 30 minutes (with oxygen 8 liters per minute or with air) 10 units of regular insulin (rapid-acting, insuline asparte, intravenous injection) as an intravenous bolus with 500 ml of 10% dextrose in water administered over a 30-minute period.

Insuline + dextrose

Patients in the experimental group will receive : 10 units of regular insulin (rapid-acting, insuline asparte, intravenous injection) as an intravenous bolus with 500 ml of 10% dextrose in water administered over a 30-minute period

Group Type: ACTIVE_COMPARATOR

Insulin Aspart

Intervention Type: DRUG

Patients in the experimental group will receive either:

1. 10 mg of salbutamol nebulized in 30 minutes (with oxygen 8 liters per minute or with air); OR

2. 10 units of regular insulin (rapid-acting, insuline asparte, intravenous injection) as an intravenous bolus with 500 ml of 10% dextrose in water administered over a 30-minute period plus 10 mg of salbutamol nebulized in 30 minutes (with oxygen 8 liters per minute or with air). The nurse will start by giving the 10 units of insulin and the dextrose, and then, immediately, she will start the nebulization of salbutamol.

Insuline + Dextrose + Salbutamol

Patients in the experimental group will receive either:

1. 10 mg of salbutamol nebulized in 30 minutes (with oxygen 8 liters per minute or with air); OR

2. 10 units of regular insulin (rapid-acting, insuline asparte, intravenous injection) as an intravenous bolus with 500 ml of 10% dextrose in water administered over a 30-minute period plus 10 mg of salbutamol nebulized in 30 minutes (with oxygen 8 liters per minute or with air). The nurse will start by giving the 10 units of insulin and the dextrose, and then, immediately, she will start the nebulization of salbutamol.

Group Type: EXPERIMENTAL

Salbutamol

Intervention Type: DRUG

10 mg of salbutamol nebulized in 30 minutes (with oxygen 8 liters per minute or with air) 10 units of regular insulin (rapid-acting, insuline asparte, intravenous injection) as an intravenous bolus with 500 ml of 10% dextrose in water administered over a 30-minute period.

Insulin Aspart

Intervention Type: DRUG

Patients in the experimental group will receive either:

1. 10 mg of salbutamol nebulized in 30 minutes (with oxygen 8 liters per minute or with air); OR

2. 10 units of regular insulin (rapid-acting, insuline asparte, intravenous injection) as an intravenous bolus with 500 ml of 10% dextrose in water administered over a 30-minute period plus 10 mg of salbutamol nebulized in 30 minutes (with oxygen 8 liters per minute or with air). The nurse will start by giving the 10 units of insulin and the dextrose, and then, immediately, she will start the nebulization of salbutamol.

Interventions

Salbutamol

10 mg of salbutamol nebulized in 30 minutes (with oxygen 8 liters per minute or with air) 10 units of regular insulin (rapid-acting, insuline asparte, intravenous injection) as an intravenous bolus with 500 ml of 10% dextrose in water administered over a 30-minute period.

Intervention Type: DRUG

Insulin Aspart

Patients in the experimental group will receive either:

1. 10 mg of salbutamol nebulized in 30 minutes (with oxygen 8 liters per minute or with air); OR

2. 10 units of regular insulin (rapid-acting, insuline asparte, intravenous injection) as an intravenous bolus with 500 ml of 10% dextrose in water administered over a 30-minute period plus 10 mg of salbutamol nebulized in 30 minutes (with oxygen 8 liters per minute or with air). The nurse will start by giving the 10 units of insulin and the dextrose, and then, immediately, she will start the nebulization of salbutamol.

Intervention Type: DRUG

Other Intervention Names

Salbutamol and Hyperkaliemia; Insulin and Hyperkaliemia

Eligibility Criteria

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 5,5 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nantes University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Julie CONTENTI

Role: PRINCIPAL_INVESTIGATOR

Nice University Hopsital

Pierre-Clément THIEBAUD

Role: PRINCIPAL_INVESTIGATOR

Saint Antoine University Hospital

Maxime MAIGNAN

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Grenoble

Jeannot SCHMIDT

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Clermont-Ferrand

Meïssa KARE

Role: PRINCIPAL_INVESTIGATOR

Agen Hospital

Tahar CHOUIHED

Role: PRINCIPAL_INVESTIGATOR

Central Hospital, Nancy, France

Anne-Laure FERAL-PIERSSENS

Role: PRINCIPAL_INVESTIGATOR

Avicenne University Hospital

Florent MAILLET

Role: PRINCIPAL_INVESTIGATOR

Louis Mourier Hospital

Quentin DELANNOY

Role: PRINCIPAL_INVESTIGATOR

La Pitié Salpetrière University Hospital

Nicolas MARJANOVIC

Role: PRINCIPAL_INVESTIGATOR

Poitiers University Hospital

delphine DOUILLET

Role: PRINCIPAL_INVESTIGATOR

Angers University Hospital

Paul-Louis MARTIN

Role: PRINCIPAL_INVESTIGATOR

Tours University Hospital

Pierrick LE BORGNE

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Strasbourg, France

Xavier EYER

Role: PRINCIPAL_INVESTIGATOR

Lariboisière Hospital

Nicolas PESCHANSKI

Role: PRINCIPAL_INVESTIGATOR

Rennes University Hospital

Locations

Agen Hospital

Agen, , France

Site Status: RECRUITING

Angers University Hospital

Angers, , France

Site Status: RECRUITING

Avicenne University Hospital

Bobigny, , France

Site Status: ACTIVE_NOT_RECRUITING

University Hospital, Clermont-Ferrand

Clermont-Ferrand, , France

Site Status: RECRUITING

Louis Mourier Hospital

Colombes, , France

Site Status: ACTIVE_NOT_RECRUITING

University Hospital, Grenoble

Grenoble, , France

Site Status: RECRUITING

Nancy University Hospital

Nancy, , France

Site Status: RECRUITING

Nantes University Hospital

Nantes, , France

Site Status: RECRUITING

Nice University Hospital

Nice, , France

Site Status: ACTIVE_NOT_RECRUITING

La Pitié Salpêtrière University Hospital

Paris, , France

Site Status: RECRUITING

Lariboisiere Hospital

Paris, , France

Site Status: RECRUITING

Saint Antoine University Hospital

Paris, , France

Site Status: RECRUITING

Poitiers University Hospital

Poitiers, , France

Site Status: RECRUITING

Rennes University Hospital

Rennes, , France

Site Status: RECRUITING

Strasbourg University Hospital

Strasbourg, , France

Site Status: ACTIVE_NOT_RECRUITING

Tours University Hospital

Tours, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Emmanuel MONTASSIER

Role: CONTACT

emmanuel.montassier@chu-nantes.fr

02 53 48 20 38

Facility Contacts

Albert TRINC DUC

Role: primary

Delphine DOUILLET

Role: primary

Jeannot SCHMIDT

Role: primary

Maxime MAIGNAN

Role: primary

Tahar CHOUIHED

Role: primary

Emmanuel Montassier

Role: primary

Yonathan FREUND

Role: primary

Xavier EYER

Role: primary

Pierre-Clément THIEBAUD

Role: primary

Olivier MIMOZ

Role: primary

Nicolas Peschanski, PhD

Role: primary

Paul-Louis MARTIN

Role: primary

References

Montassier E, Lemoine L, Hardouin JB, Rossignol P, Legrand M. Insulin glucose infusion versus nebulised salbutamol versus combination of salbutamol and insulin glucose in acute hyperkalaemia in the emergency room: protocol for a randomised, multicentre, controlled study (INSAKA). BMJ Open. 2020 Aug 26;10(8):e039277. doi: 10.1136/bmjopen-2020-039277.

Reference Type: DERIVED

PMID: 32847923 (View on PubMed)

Other Identifiers

RC19_0048

Identifier Type: -

Identifier Source: org_study_id