Comparison of a Low Dose to a Standard Dose of Insulin in Adult DKA in ICU to Reduce Metabolic Complications

NCT ID: NCT05443802

Last Updated: 2025-05-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-16
• Study Completion Date: 2025-03-31

Brief Summary

Diabetic ketoacidosis (DKA), a frequent complication of diabetes, is the consequence of a profound insulin deficiency responsible for osmotic polyuria and thus major losses of water, glucose, sodium and potassium as well as a metabolic acidosis due to the uncontrolled production of ketonic acids. Management includes fluid replacement, insulin therapy and correction of metabolic disorders (including potassium loss).

Initially described in patients with type 1 diabetes (T1D), it is now often observed in patients with type 2 diabetes (T2D) in whom it is more a matter of insulin resistance than an absolute deficiency. However, international guidelines recommend a similar dose of intravenous insulin (0.10 IU/kg/hour) regardless of the type of diabetes.

During treatment, metabolic complications are frequent and potentially serious, especially in T2D due to cardiovascular comorbidities.

The research hypothesis is that decreasing the insulin dose will reduce metabolic complications without influencing time to resolution in adult patients, regardless of diabetes type.

Detailed Description

Diabetic ketoacidosis (DKA), a frequent complication of diabetes, is the consequence of a profound insulin deficiency responsible for osmotic polyuria which leads to major losses of water, sodium and potassium as well as the generation of metabolic acidosis due to the uncontrolled production of ketonic acids. Management includes fluid replacement, insulin therapy and correction of metabolic disorders (including potassium loss and acidosis).

Initially described in patients with type 1 diabetes (T1D), it is now often observed in patients with type 2 diabetes (T2D) in whom it is more insulin resistance than absolute deficiency. However, international guidelines recommend a similar dosage of intravenous insulin (0.10 IU/kg/hour) regardless of the type of diabetes.

During treatment, metabolic complications are frequent and potentially serious, especially in T2D due to cardiovascular comorbidities.

A British study reported 27.6% hypoglycaemia and 55% hypokalemia during the first 24 hours of treatment. Comparable figures were observed by conducting a multicenter retrospective study of 122 patients: hypokalaemia and hypoglycaemia were observed in nearly two thirds of cases.

A pediatric study showed that a lower dose of insulin (0.05 IU/kg/h) reduced the rate of hypoglycaemia (20% vs 4%) and hypokalaemia (48% vs 20%) compared to at the standard dose (0.10 IU/kg/h) without modifying the time to resolution. But the very small number (25 children per arm), the questionable statistical analysis and the pediatric population (T1D only) do not make it possible to anticipate the potential benefit in a much more heterogeneous adult population.

The hypothesis of the research is that decreasing the insulin dose will reduce metabolic complications without influencing time to resolution in adult patients, regardless of diabetes type.

Conditions

Diabetic Ketoacidosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Experimental

Reduced dose of rapid-acting insulin of 0.05 IU/kg/h from randomization until resolution of DKA

Group Type: EXPERIMENTAL

Insulin 0.05 IU/kg/h

Intervention Type: DRUG

In the experimental arm, the patients will be given an insulin dose of 0.05 IU/kg/h.

Control

Rapid-acting insulin dose of 0.10 IU/kg/h in accordance with usual recommendations until resolution of DKA

Group Type: OTHER

Insulin 0.10 IU/kg/h

Intervention Type: DRUG

In the control arm, patients will receive an insulin dose of 0.10 IU/kg/h.

Interventions

Insulin 0.05 IU/kg/h

In the experimental arm, the patients will be given an insulin dose of 0.05 IU/kg/h.

Intervention Type: DRUG

Insulin 0.10 IU/kg/h

In the control arm, patients will receive an insulin dose of 0.10 IU/kg/h.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patient aged 18 years or above
• Admission in Intense/Intermediate Care Unit
• Severe DKA due to all types of diabetes (T1D, T2D and secondary diabetes and inaugural ketoacidosis) defined by association of the following 3 parameters:
• glucose > 11 mmol/L or affirmation of having diabetes
• ketonemia > 3mmol/L or ketonuria ≥ 2
• bicarbonate < 15 mmol/L and/or venous pH < or=7.3
• Randomization possible before 15UI of insulin administrated in total
• Informed and written consent. In the absence of parent/ relative/ person of trust, the patient may be included via the emergency procedure and consent will be obtained as soon as possible

Exclusion Criteria

• Non-diabetic ketoacidosis (fasting or alcoholic)
• Patient weighing less than 30 kg
• Hypokalemia < 3.5 mmol/L at the time of inclusion
• Hyperosmolar hyperglycemic state (defined as efficient plasma osmolarity > 320 mosmol/L)
• Absence of social security coverage
• Pregnant or breastfeeding patient
• Patient under tutelage or curators
• Patient deprived of liberty due to a judicial or administrative decision
• Patient with a renal disease requiring dialysis
• Acute or chronic liver failure with Factor V < 50%
• Patient receiving a high dose of corticosteroids (≥ 0.5 mg/kg) daily
• Patient included in another interventional study

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

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Damien Roux, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Louis Mourier Hospital

Colombes, , France

Countries

France

Other Identifiers

APHP210081

Identifier Type: -

Identifier Source: org_study_id