Basal Insulin in the Management of Patients With DKA - Full Text View

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 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

MedlinePlus related topics:

Diabetes

ChemIDplus related topics:

Insulin Insulin glargine Insulin glulisine

U.S. FDA Resources

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

Further study details as provided by Emory University:

Primary Outcome Measures:

The primary outcome of the study is to determine differences in glycemic control as measured by mean daily blood glucose concentration between treatment groups once DKA has resolved and the insulin drip is discontinued. [ Time Frame: BG acqhs ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

differences between treatment groups in any of the following measures: number of hypoglycemic events (blood glucose < 60 mg/dl) between hours 12 to 36 (second day), number of hyperglycemic episodes (blood glucose > 200 mg/dl). [ Time Frame: BG acqhs and prn ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	80
Study Start Date:	September 2006
Study Completion Date:	June 2008
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Daily insulin glargine (Lantus) + glulisine (Apidra) before meals	Drug: insulin glargine+ glulisine Daily insulin glargine + glulisine before meals
2: 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

Responsible Party:	Emory Univ SOM ( Guillermo Umpierrez, MD/Principal Investigator )
Study ID Numbers:	790-2006
First Received:	December 28, 2007
Last Updated:	August 19, 2008
ClinicalTrials.gov Identifier:	NCT00590044
Health Authority:	United States: Institutional Review Board

Keywords provided by Emory University:

Diabetic ketoacidosis

insulin therapy

DKA

Study placed in the following topic categories:

Insulin glulisine

Metabolic Diseases

Glargine

Diabetes Mellitus

Endocrine System Diseases

Diabetic Ketoacidosis

Endocrinopathy

Metabolic disorder

Glucose Metabolism Disorders

Insulin

Diabetes Complications

Acidosis

Additional relevant MeSH terms:

Hypoglycemic Agents

Physiological Effects of Drugs

Pharmacologic Actions

Acid-Base Imbalance

ClinicalTrials.gov processed this record on October 10, 2008

Sponsors and Collaborators:	Emory University Sanofi-Aventis
Information provided by:	Emory University
ClinicalTrials.gov Identifier:	NCT00590044