Clinical trial NCT00590044: Basal Insulin in the Management of Patients With Diabetic Ketoacidosis (DKA)
Official title: Basal Insulin in the Management of Patients With Diabetic Ketoacidosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetic Ketoacidosis
Keywords: Diabetic ketoacidosis
insulin therapy
DKA
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2008-01-10
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is a multicenter, randomized controlled trial to compare the safety and efficacy of insulin analogs and human insulins both during acute intravenous treatment and during the transition to subcutaneous insulin in patients with diabetic ketoacidosis (DKA).

Detailed description: Diabetic ketoacidosis (DKA) is the most serious emergency in patients with diabetes. With an estimated 100,000 admissions per year in the United States, DKA is also the leading cause of death in children with type 1 diabetes, and accounts for a significant proportion of admissions in adult patients with type 1 and type 2 diabetes. The mainstay in the treatment of DKA involves the continuous intravenous (IV) infusion of regular insulin or the frequent subcutaneous (SC) injections of regular or rapid-acting insulin analogs. Multiple studies have reported successful protocols for insulin administration during the acute management of DKA, but they have failed to address the transition phase from IV to SC maintenance insulin regimen. The American Diabetes Association (ADA) position statement recommends the use of split-mixed insulin combination of regular and intermediate-acting insulin (NPH). This regimen, however, are associated with a high rate of hyperglycemia shortly after discontinuation of IV insulin and a risk of hypoglycemia during the hospital stay. Recently, the long-acting "basal" insulin glargine (Lantus®, Sanofi Aventis Pharmaceuticals) has been shown to facilitate glycemic control with lower rate of hypoglycemic events than intermediate-acting insulin in subjects with type 1 and type 2 diabetes. This study aims i) to determine the effects of giving a dose of glargine insulin shortly after starting an intravenous insulin infusion on glycemic control, time to resolve DKA, and rate of hypoglycemia in patients with DKA, and ii) to compare the safety and efficacy of basal/bolus (glargine/glulisine) insulin versus the standard split-mixed insulin regimen of NPH and regular insulin after the resolution of DKA. The hypothesis is that basal (lantus®) insulin as compared to NPH insulin shortly after the start of insulin infusion will improve inpatient glycemic control in patients with DKA.

Eligibility criteria: Inclusion Criteria:

* All patients admitted to Grady Memorial Hospital who meet diagnosis criteria of DKA and who are willing to participate in the study protocol will be considered candidates for inclusion into the study.
* Diagnostic Criteria for DKA: Blood glucose \> 250 mg/dL, arterial or venous phenol hydroxylase (pH) \< 7.3, serum bicarbonate \< 18 milliequivalent/L, and moderate to severe ketonemia (acetoacetate ≥ 1:4 or βeta-hydroxybutyrate \> 3 mmol).

Exclusion Criteria:

* Hemodynamic instability (MAP \< 50 or patients requiring pressor)
* Significant identifiable medical or surgical illness, including but not limited to: acute myocardial infarction, congestive heart failure; respiratory failure requiring mechanical ventilation; acute or chronic renal insufficiency (serum creatinine \> 3.0 mg/dl); end stage liver failure, and cirrhosis.
* Patients with dementia or persistent altered mental status that would prevent collection of consent form and reliable information.
* Pregnancy

Primary outcomes:
measure: Number of Hypoglycemia Episodes After the Transition Period From Intravenous Insulin to Subcutaneous Insulin Between 2 Treatment Groups
timeFrame: 5 days after transitioning to subcutaneous insulin
Secondary outcomes:
measure: Mean Daily Blood Glucose Concentration Between the Two Groups After the Resolution of Ketoacidosis and Transition to Subcutaneous Insulin
timeFrame: Day1 - Day5 after the resolution of ketoacidosis and transition to subcutaneous insulin
measure: Mean Blood Glucose Concentration in mg/dL While on the Insulin Drip Among the 2 Groups
timeFrame: up to 20 hours
measure: Difference in Time in Hours to Resolution of DKA Between the 2 Groups
timeFrame: up to 20 hours
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Minneapolis
country: United States
facility: University of Minnesota School of Medicine
state: Minnesota
Study officials:
affiliation: Emory University SOM
name: Guillermo Umpierrez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota
name: Sidney Jones, MD
role: STUDY_CHAIR
References:
citation: Umpierrez GE, Jones S, Smiley D, Mulligan P, Keyler T, Temponi A, Semakula C, Umpierrez D, Peng L, Ceron M, Robalino G. Insulin analogs versus human insulin in the treatment of patients with diabetic ketoacidosis: a randomized controlled trial. Diabetes Care. 2009 Jul;32(7):1164-9. doi: 10.2337/dc09-0169. Epub 2009 Apr 14.