Trial Outcomes & Findings for Basal Insulin in the Management of Patients With Diabetic Ketoacidosis (DKA) (NCT NCT00590044)

Results Overview

To determine the safety of the two treatments the number of hypoglycemia episodes that occurred between the 2 groups are measured from the time of transitioning to subcutaneous insulin to day 5. The hypoglycemia events are defined as blood glucose levels \<70 mg/dL. The results were obtained from the citation Umpierrez GE, Jones S, Smiley D, Mulligan P, Keyler T, Temponi A, Semakula C, Umpierrez D, Peng L, Cerón 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. PubMed ID: 19366972.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

74 participants

Primary outcome timeframe

5 days after transitioning to subcutaneous insulin

Results posted on

2018-09-26

Participant Flow

This study was conducted at Grady Memorial Hospital, Atlanta, Georgia, and at Hennepin County Medical Center, Minneapolis, Minnesota

A total of 74 patients with DKA were randomly assigned. Of them, 6 were excluded because 4 withdrew consent before or shortly after initiation of insulin therapy, one patient received glargine insulin before resolution of DKA, and one patient was treated with IV aspart insulin instead of regular insulin. The remaining 68 were included in analysis

Participant milestones

Participant milestones
Measure	Glargine (Lantus) + Glulisine Daily insulin glargine (Lantus) + glulisine (Apidra) before meals	NPH + Regular Split-mixed NPH + Regular insulin twice daily
Overall Study STARTED	38	36
Overall Study COMPLETED	34	34
Overall Study NOT COMPLETED	4	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Glargine (Lantus) + Glulisine Daily insulin glargine (Lantus) + glulisine (Apidra) before meals	NPH + Regular Split-mixed NPH + Regular insulin twice daily
Overall Study Withdrawal by Subject	2	2
Overall Study wrong insulin arm assigned	1	0
Overall Study Protocol Violation	1	0

Baseline Characteristics

Basal Insulin in the Management of Patients With Diabetic Ketoacidosis (DKA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Glargine (Lantus) + Glulisine n=38 Participants Daily insulin glargine (Lantus) + glulisine (Apidra) before meals	NPH + Regular n=36 Participants Split-mixed NPH + Regular insulin twice daily	Total n=74 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	38 Participants n=93 Participants	36 Participants n=4 Participants	74 Participants n=27 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Continuous	39 years STANDARD_DEVIATION 12 • n=93 Participants	38 years STANDARD_DEVIATION 12 • n=4 Participants	38.5 years STANDARD_DEVIATION 12 • n=27 Participants
Sex: Female, Male Female	14 Participants n=93 Participants	12 Participants n=4 Participants	26 Participants n=27 Participants
Sex: Female, Male Male	24 Participants n=93 Participants	24 Participants n=4 Participants	48 Participants n=27 Participants
Region of Enrollment United States	38 participants n=93 Participants	36 participants n=4 Participants	74 participants n=27 Participants

PRIMARY outcome

Timeframe: 5 days after transitioning to subcutaneous insulin

To determine the safety of the two treatments the number of hypoglycemia episodes that occurred between the 2 groups are measured from the time of transitioning to subcutaneous insulin to day 5. The hypoglycemia events are defined as blood glucose levels \<70 mg/dL. The results were obtained from the citation Umpierrez GE, Jones S, Smiley D, Mulligan P, Keyler T, Temponi A, Semakula C, Umpierrez D, Peng L, Cerón 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. PubMed ID: 19366972.

Outcome measures

Outcome measures
Measure	Insulin Glargine+Glulisine n=34 Participants Daily insulin glargine + glulisine before meals insulin glargine+ glulisine: Daily insulin glargine + glulisine before meals	Split-mixed NPH + Regular Insulin n=34 Participants Split-mixed NPH + Regular insulin twice daily NPH + Regular insulin: Split-mixed NPH + Regular insulin twice daily
Number of Hypoglycemia Episodes After the Transition Period From Intravenous Insulin to Subcutaneous Insulin Between 2 Treatment Groups	8 number of hypoglycemia episodes	26 number of hypoglycemia episodes

SECONDARY outcome

Timeframe: Day1 - Day5 after the resolution of ketoacidosis and transition to subcutaneous insulin

The primary outcome during the subcutaneous (SC) period (the primary outcome measurement) was to determine differences in glycemic control as measured by mean daily blood glucose(BG) concentration between treatment groups. The results were obtained from the citation Umpierrez GE, Jones S, Smiley D, Mulligan P, Keyler T, Temponi A, Semakula C, Umpierrez D, Peng L, Cerón 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. PubMed Identification (ID): 19366972.

Outcome measures

Outcome measures
Measure	Insulin Glargine+Glulisine n=34 Participants Daily insulin glargine + glulisine before meals insulin glargine+ glulisine: Daily insulin glargine + glulisine before meals	Split-mixed NPH + Regular Insulin n=34 Participants Split-mixed NPH + Regular insulin twice daily NPH + Regular insulin: Split-mixed NPH + Regular insulin twice daily
Mean Daily Blood Glucose Concentration Between the Two Groups After the Resolution of Ketoacidosis and Transition to Subcutaneous Insulin Day 1	213 mg/dl Standard Deviation 76	188 mg/dl Standard Deviation 61
Mean Daily Blood Glucose Concentration Between the Two Groups After the Resolution of Ketoacidosis and Transition to Subcutaneous Insulin Day 2	220 mg/dl Standard Deviation 61	206 mg/dl Standard Deviation 71
Mean Daily Blood Glucose Concentration Between the Two Groups After the Resolution of Ketoacidosis and Transition to Subcutaneous Insulin Day 3	180 mg/dl Standard Deviation 80	207 mg/dl Standard Deviation 86
Mean Daily Blood Glucose Concentration Between the Two Groups After the Resolution of Ketoacidosis and Transition to Subcutaneous Insulin Day 4	158 mg/dl Standard Deviation 44	211 mg/dl Standard Deviation 63
Mean Daily Blood Glucose Concentration Between the Two Groups After the Resolution of Ketoacidosis and Transition to Subcutaneous Insulin Day 5	124 mg/dl Standard Deviation 41	190 mg/dl Standard Deviation 45

SECONDARY outcome

Timeframe: up to 20 hours

To determine the differences in glycemic control as measured by differences in the mean daily blood glucose levels between treatment groups (insulin drip with regular insulin vs glulisine insulin) during the acute phase of diabetic ketoacidosis(DKA) before transitioning to subcutaneous insulin. The results were obtained from the citation Umpierrez GE, Jones S, Smiley D, Mulligan P, Keyler T, Temponi A, Semakula C, Umpierrez D, Peng L, Cerón 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. PubMed ID: 19366972.

Outcome measures

Outcome measures
Measure	Insulin Glargine+Glulisine n=34 Participants Daily insulin glargine + glulisine before meals insulin glargine+ glulisine: Daily insulin glargine + glulisine before meals	Split-mixed NPH + Regular Insulin n=34 Participants Split-mixed NPH + Regular insulin twice daily NPH + Regular insulin: Split-mixed NPH + Regular insulin twice daily
Mean Blood Glucose Concentration in mg/dL While on the Insulin Drip Among the 2 Groups	153 mg/dL Standard Deviation 61	185 mg/dL Standard Deviation 58

SECONDARY outcome

Timeframe: up to 20 hours

The mean duration of treatment until resolution of ketoacidosis is measured and compared between the 2 groups. The DKA was considered resolved when blood glucose was 250 mg/dl, the serum bicarbonate level was \<18 mmol/l, and venous phenol hydroxylase (pH) was 7.30. The results were obtained from the citation Umpierrez GE, Jones S, Smiley D, Mulligan P, Keyler T, Temponi A, Semakula C, Umpierrez D, Peng L, Cerón 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. PubMed ID: 19366972.

Outcome measures

Outcome measures
Measure	Insulin Glargine+Glulisine n=34 Participants Daily insulin glargine + glulisine before meals insulin glargine+ glulisine: Daily insulin glargine + glulisine before meals	Split-mixed NPH + Regular Insulin n=34 Participants Split-mixed NPH + Regular insulin twice daily NPH + Regular insulin: Split-mixed NPH + Regular insulin twice daily
Difference in Time in Hours to Resolution of DKA Between the 2 Groups	8.9 hours Standard Deviation 4.7	10.5 hours Standard Deviation 6.3

Adverse Events

Glargine (Lantus) + Glulisine

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

NPH + Regular

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Glargine (Lantus) + Glulisine n=38 participants at risk Daily insulin glargine (Lantus) + glulisine (Apidra) before meals	NPH + Regular n=36 participants at risk Split-mixed NPH + Regular insulin twice daily
Endocrine disorders Severe Hypoglycemia	2.6% 1/38 • Number of events 1 • The adverse event data are collected from the time of admission to day 5 after the resolution of diabetic ketoacidosis (DKA). For this study the adverse events of interest were hypoglycemia events where glucose levels are \<70 mg/dL and severe hypoglycemia events with glucose level \<40 mg/dL. The events were collected from rom the time of admission to day 5 after the resolution of diabetic ketoacidosis (DKA). The rest of the treatments for the patients was standard of care treatment.	5.6% 2/36 • Number of events 2 • The adverse event data are collected from the time of admission to day 5 after the resolution of diabetic ketoacidosis (DKA). For this study the adverse events of interest were hypoglycemia events where glucose levels are \<70 mg/dL and severe hypoglycemia events with glucose level \<40 mg/dL. The events were collected from rom the time of admission to day 5 after the resolution of diabetic ketoacidosis (DKA). The rest of the treatments for the patients was standard of care treatment.

Other adverse events

Other adverse events
Measure	Glargine (Lantus) + Glulisine n=38 participants at risk Daily insulin glargine (Lantus) + glulisine (Apidra) before meals	NPH + Regular n=36 participants at risk Split-mixed NPH + Regular insulin twice daily
Endocrine disorders Hypoglycemia	13.2% 5/38 • Number of events 8 • The adverse event data are collected from the time of admission to day 5 after the resolution of diabetic ketoacidosis (DKA). For this study the adverse events of interest were hypoglycemia events where glucose levels are \<70 mg/dL and severe hypoglycemia events with glucose level \<40 mg/dL. The events were collected from rom the time of admission to day 5 after the resolution of diabetic ketoacidosis (DKA). The rest of the treatments for the patients was standard of care treatment.	38.9% 14/36 • Number of events 26 • The adverse event data are collected from the time of admission to day 5 after the resolution of diabetic ketoacidosis (DKA). For this study the adverse events of interest were hypoglycemia events where glucose levels are \<70 mg/dL and severe hypoglycemia events with glucose level \<40 mg/dL. The events were collected from rom the time of admission to day 5 after the resolution of diabetic ketoacidosis (DKA). The rest of the treatments for the patients was standard of care treatment.

Additional Information

Guillermo Umpierrez

Emory University SOM

Phone: 4047781663

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place