Clinical trial NCT05443802: Comparison of a Low Dose to a Standard Dose of Insulin in Adult DKA in ICU to Reduce Metabolic Complications
Official title: Comparison of a Low Dose to a Standard Dose of Insulin in Adult Diabetic Ketoacidosis in ICU to Reduce Metabolic Complications : a Randomized, Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetic Ketoacidosis
Keywords: Diabetic ketoacidosis
Insulin deficiency
Hypoglycemia
Hypokalemia
Metabolic complications
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2022-07-05
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Metabolic complications
timeFrame: 48 hours
Secondary outcomes:
measure: Resolution of diabetic ketoacidosis
timeFrame: 48 hours
measure: Episode of hypokalaemia
timeFrame: 48 hours
measure: Episode of hypoglycemia
timeFrame: 48 hours
measure: Episode of severe hypoglycemia
timeFrame: 48 hours
measure: Cardiac arrythmia diagnosed by EKG
timeFrame: 48 hours
measure: Glucose infusion 1000mL
timeFrame: 48 hours
measure: Glucose infusion of 30% glucose solution
timeFrame: 48 hours
measure: Amount of glucose perfused
timeFrame: 48 hours
measure: Potassium intake
timeFrame: 48 hours
measure: Length of stay in ICU
timeFrame: 48 hours
measure: Time between patient randomization and resolution of DKA in T1D population
timeFrame: 48 hours
measure: Time between patient randomization and resolution of DKA in T2D population
timeFrame: 48 hours
measure: Time between patient randomization and resolution of DKA in patients suffering from first ketoacidosis episode
timeFrame: 48 hours
measure: Episode of hypokalaemia in T1D population
timeFrame: 48 hours
measure: Episode of hypokalaemia in T2D population
timeFrame: 48 hours
measure: Episode of hypokalaemia in patients suffering from first ketoacidosis episode
timeFrame: 48 hours
measure: Episode of hypoglycaemia in T1D population
timeFrame: 48 hours
measure: Episode of hypoglycaemia in T2D population
timeFrame: 48 hours
measure: Episode of hypoglycaemia in patients suffering from first ketoacidosis episode
timeFrame: 48 hours
measure: Episode of severe hypoglycaemia in T1D population
timeFrame: 48 hours
measure: Episode of severe hypoglycaemia in T2D population
timeFrame: 48 hours
measure: Episode of severe hypoglycaemia in patients suffering from first ketoacidosis episode
timeFrame: 48 hours
Other outcomes:
Locations:
city: Colombes
country: France
facility: Louis Mourier Hospital
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Damien Roux, PhD
role: PRINCIPAL_INVESTIGATOR
References: