Basal Insulin in the Management of Patients With Diabetic Ketoacidosis (DKA) - Full Text View

Sponsor:	Emory University
Collaborator:	Sanofi-Aventis
Information provided by:	Emory University
ClinicalTrials.gov Identifier:	NCT00590044

Purpose

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.

This investigator initiated research will be conducted at Grady Memorial Hospital, Atlanta and at University of Minnesota, MN. Dr Umpierrez designed the study and will serve as principal investigator. A total of 40 patients will be recruited at each site.

Condition	Intervention	Phase
Diabetic Ketoacidosis	Drug: insulin glargine+ glulisine Drug: NPH + Regular insulin	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title:	Basal Insulin in the Management of Patients With Diabetic Ketoacidosis

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Hypoglycemia

Drug Information available for: Insulin Insulin glargine

U.S. FDA Resources

Further study details as provided by Emory University:

Primary Outcome Measures:

Mean Daily Blood Glucose Concentration After the Resolution of DKA [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Mean Daily Blood Glucose Concentration While on the Insulin Drip [ Time Frame: blood glucose (BG) before meals and at bedtime ] [ Designated as safety issue: No ]
Frequency of Hypoglycemia [ Time Frame: blood glucose (BG) before meals, at bedtime and as needed ] [ Designated as safety issue: Yes ]
Frequency of Hyperglycemia [ Time Frame: blood glucose (BG) before meals, at bedtime and as needed ] [ Designated as safety issue: Yes ]

Enrollment:	74
Study Start Date:	December 2007
Study Completion Date:	August 2008
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
glargine (Lantus) + glulisine (Apidra): Experimental Daily insulin glargine (Lantus) + glulisine (Apidra) before meals	Drug: insulin glargine+ glulisine Daily insulin glargine + glulisine before meals
Split-mixed NPH + Regular insulin: Active Comparator Split-mixed NPH + Regular insulin twice daily	Drug: NPH + Regular insulin Split-mixed NPH + Regular insulin twice daily

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 pH < 7.3, serum bicarbonate < 18 mEq/L, and moderate to severe ketonemia (acetoacetate ≥ 1:4 or β-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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00590044

Locations

United States, Georgia
Grady Memorial Hospital
Atlanta, Georgia, United States, 30303
United States, Minnesota
University of Minnesota School of Medicine
Minneapolis, Minnesota, United States, 55455

Sponsors and Collaborators

Emory University

Sanofi-Aventis

Investigators

Principal Investigator:	Guillermo Umpierrez, MD	Emory University SOM
Study Chair:	Sidney Jones, MD	University of Minnesota

More Information

No publications provided

Responsible Party:	Emory Univ SOM ( Guillermo Umpierrez, MD/Principal Investigator )
Study ID Numbers:	790-2006
Study First Received:	December 28, 2007
Results First Received:	January 30, 2009
Last Updated:	May 18, 2009
ClinicalTrials.gov Identifier:	NCT00590044 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Emory University:

Diabetic ketoacidosis
insulin therapy
DKA

Additional relevant MeSH terms:

Metabolic Diseases
Physiological Effects of Drugs
Diabetes Mellitus
Endocrine System Diseases
Acidosis
Acid-Base Imbalance
Insulin

Pharmacologic Actions
Hypoglycemic Agents
Glargine
Diabetic Ketoacidosis
Glucose Metabolism Disorders
Diabetes Complications

ClinicalTrials.gov processed this record on November 30, 2009