Diabetic Ketoacidosis, Type 1 Diabetes, Type 2 Diabetes
Conditions
Brief summary
Early Basal Insulin Administration in Adult Diabetic Ketoacidosis Management
Detailed description
The transition from IV Insulin Infusion (IVII) to Subcutaneous Long-acting insulin injections in Diabetic Ketoacidosis (DKA) management frequently results in rebound hyperglycemia, particularly if there are high insulin requirements that can adversely affect the DKA recovery, increase Length Of Stay (LOS), morbidity, and mortality. Investigators propose a prospective, open-label, intervention, non-randomized, controlled study to test the hypothesis that an insulin glargine dose of 0.4 Units/kg early administered (within four hours) of IVII initiation in DKA management in adult would be effective and safe in shortening the time to anion gap closure comparing to the standard practice.
Interventions
DRUGEarly Glargine
A dose of insulin glargine, 0.4 unit/kg, will be given within 4 hours from initiating the IV Insulin Infusion
DRUGLate Glargine
A historical retrospective control group for the adult patients admitted to the same ICU with a diagnosis of DKA and received insulin glargine after anion gap closure.
OTHERIV insulin infusion
Continuous weight based IV insulin infusion as per Cleveland Clinic DKA Protocol
OTHERIV fluid and electrolytes replacement
The IV fluid and electrolytes replacement will be left to the treating physician's discretion. IV fluid to contain dextrose to keep Target Blood Glucose 150 - 200 mg/dl during the DKA management and 140 - 180 mg/dl after DKA resolution.
Sponsors
The Cleveland Clinic
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years old * Meet DKA definition (BG ≥ 250 mg/dl, Anion Gap \> 12 mEq/L, and positive Ketones in serum or urine) * Having the capacity to sign Informed consent
Exclusion criteria
* IV insulin infusion was initiated for more than 4 hours. * Persistent hypotension (SBP\<80 mmHg despite receiving 1000cc normal saline). * Require Vasopressor * Acute Coronary Syndrome * Pregnant * End-stage renal disease * Unwilling to consent to participate in the trial * Currently under police custody * Transferred from another hospital * Require emergent surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Anion Gap Closure | Participants monitored from hospital admission to discharge, an average of 5 days | Measured in hours from starting insulin infusion till anion gap ≤ 12 milliequivalent/Liter (mEq/L) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ICU Length of Stay | Participants monitored from hospital admission to discharge, an average of 5 days | The time, in hours, from the patient admission to the ICU till transfer to regular nursing floor |
| Total IV Insulin Infusion Dose | Participants monitored from hospital admission to discharge, an average of 5 days | the total amount of insulin infusion, by International Unit, has been received by the patient during the DKA treatment |
| Hospital Length of Stay | Participants monitored from hospital admission to discharge, an average of 5 days | The time, in days, from the patient admission to the hospital till discharge |
| Incidence of Hyperglycemia | up to 24 hours after initial Insulin Glargine dose | Incidence of hyperglycemia (\> 180 mg/dL) after IVII discontinuation |
| Incidence of Hypoglycemia | up to 24 hours after initial Insulin Glargine dose | Incidence of hypoglycemia (defined as ≤ 70 mg/dL, \<54 mg/dL, \<40 mg/dl) after IVII discontinuation |
| Incidence of Transitional Failure | up to 24 hours after IVII discontinuation | Defined as the recurrence of DKA (BG ≥ 250 mg/dl, Anion Gap \> 12 milliequivalent/Liter (mEq/L), and positive Ketones in serum or urine) after initial IV insulin infusion (IVII) discontinuation within 24 hours and requiring re-initiating the IVII |
Countries
United States
Participant flow
Pre-assignment details
The study was closed due to lack of proper resource availability. Since study could not be completed as planned, no analysis was completed. This included no enrollment into the chart review arm.
Participants by arm
| Arm | Count |
|---|---|
| Early Glargine All consecutive adult patients getting admitted to Medical ICU and meet the inclusion criteria and accepted to receive insulin glargine early as per the protocol. They will receive insulin glargine 0.4 unit/kg within 4 hours from initiating the IV Insulin Infusion, as per the Cleveland Clinic DKA protocol.
Glargine: A dose of insulin glargine, 0.4 unit/kg, will be given within 4 hours from initiating the IV Insulin Infusion
IV insulin infusion: Continuous weight based IV insulin infusion as per Cleveland Clinic DKA Protocol
IV fluid and electrolytes replacement: The IV fluid and electrolytes replacement will be left to the treating physician's discretion. IV fluid to contain dextrose to keep Target Blood Glucose 150 - 200 mg/dl during the DKA management and 140 - 180 mg/dl after DKA resolution. | 39 |
| Standard Practice (Late Glargine) Retrospective, prespecified and matched sample of consecutive adults who admitted to the same Medical ICU with a diagnosis of DKA in the period between January 1st 2019 till the Institutional Review Board (IRB) approval date and didn't receive basal insulin before Anion Gap closure.
Glargine: A historical retrospective control group for the adult patients admitted to the same ICU with a diagnosis of DKA and received insulin glargine after anion gap closure.
IV insulin infusion: Continuous weight based IV insulin infusion as per Cleveland Clinic DKA Protocol
IV fluid and electrolytes replacement: The IV fluid and electrolytes replacement will be left to the treating physician's discretion. IV fluid to contain dextrose to keep Target Blood Glucose 150 - 200 mg/dl during the DKA management and 140 - 180 mg/dl after DKA resolution. | 0 |
| Total | 39 |
Baseline characteristics
| Characteristic | Total | Early Glargine | Standard Practice (Late Glargine) |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 8 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants | 31 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 10 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 29 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Black or African American | 11 Participants | 11 Participants | — |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 7 Participants | — |
| Race (NIH/OMB) White | 21 Participants | 21 Participants | — |
| Region of Enrollment United States | 39 participants | 39 participants | — |
| Sex: Female, Male Female | 20 Participants | 20 Participants | 0 Participants |
| Sex: Female, Male Male | 19 Participants | 19 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 0 |
| other Total, other adverse events | 0 / 39 | 0 / 0 |
| serious Total, serious adverse events | 0 / 39 | 0 / 0 |
Outcome results
Primary
Time to Anion Gap Closure
Measured in hours from starting insulin infusion till anion gap ≤ 12 milliequivalent/Liter (mEq/L)
Time frame: Participants monitored from hospital admission to discharge, an average of 5 days
Population: Study withdrawn. The study was closed due to lack of proper resource availability. Since study could not be completed as planned, no data was collected for analysis.
Secondary
Hospital Length of Stay
The time, in days, from the patient admission to the hospital till discharge
Time frame: Participants monitored from hospital admission to discharge, an average of 5 days
Population: Study withdrawn. The study was closed due to lack of proper resource availability. Since study could not be completed as planned, no data was collected for analysis.
Secondary
ICU Length of Stay
The time, in hours, from the patient admission to the ICU till transfer to regular nursing floor
Time frame: Participants monitored from hospital admission to discharge, an average of 5 days
Population: Study withdrawn. The study was closed due to lack of proper resource availability. Since study could not be completed as planned, no data was collected for analysis.
Secondary
Incidence of Hyperglycemia
Incidence of hyperglycemia (\> 180 mg/dL) after IVII discontinuation
Time frame: up to 24 hours after initial Insulin Glargine dose
Population: Study withdrawn. The study was closed due to lack of proper resource availability. Since study could not be completed as planned, no data was collected for analysis.
Secondary
Incidence of Hypoglycemia
Incidence of hypoglycemia (defined as ≤ 70 mg/dL, \<54 mg/dL, \<40 mg/dl) after IVII discontinuation
Time frame: up to 24 hours after initial Insulin Glargine dose
Population: Study withdrawn. The study was closed due to lack of proper resource availability. Since study could not be completed as planned, no data was collected for analysis.
Secondary
Incidence of Transitional Failure
Defined as the recurrence of DKA (BG ≥ 250 mg/dl, Anion Gap \> 12 milliequivalent/Liter (mEq/L), and positive Ketones in serum or urine) after initial IV insulin infusion (IVII) discontinuation within 24 hours and requiring re-initiating the IVII
Time frame: up to 24 hours after IVII discontinuation
Population: Study withdrawn. The study was closed due to lack of proper resource availability. Since study could not be completed as planned, no data was collected for analysis.
Secondary
Total IV Insulin Infusion Dose
the total amount of insulin infusion, by International Unit, has been received by the patient during the DKA treatment
Time frame: Participants monitored from hospital admission to discharge, an average of 5 days
Population: Study withdrawn. The study was closed due to lack of proper resource availability. Since study could not be completed as planned, no data was collected for analysis.