Clinical trial NCT01136746: Hospital Management of Hyperglycemia Study of Insulin Glargine Plus Insulin Lispro Versus Human Regular Insulin
Official title: Randomized Clinical Trial of Subcutaneous Analog Basal Bolus Therapy Versus Sliding Scale Human Regular Insulin in the Hospital Management of Hyperglycemia in Non-Critically Ill Patients Without Known History of Diabetes: The HMH Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hyperglycemia
Keywords: Hyperglycemia
Diabetes
Hospital
Diabetic
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-06-03
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the use of insulin glargine plus insulin lispro to human regular insulin for treatment of hyperglycemia in the hospital setting in patients without known prior history of diabetes.

Detailed description: This study involves a comparison of 2 methods for administering subcutaneous insulin therapy to non-critically ill adult patients with hyperglycemia and without known history of diabetes who are admitted to non-intensive care unit (ICU) general medical hospital services. Basal-bolus therapy, considered the gold standard for glucose control in patients with known diabetes, will be compared with sliding scale insulin, a commonly used method of glucose control (prevailing standard practice) in hospitalized patients. In this study, basal-bolus therapy will consist of once-daily glargine plus lispro 3 to 4 times daily adjusted to achieve pre-meal capillary plasma glucose \<140 milligrams per deciliter (mg/dL) and bedtime capillary plasma glucose \<180 mg/dL for patients who are eating \[predose plasma glucose \<140 mg/dL for patients with nil per os (NPO) orders\]; sliding scale insulin will be administered using human regular insulin 4 times daily as needed adjusted to achieve predose capillary plasma glucose target \<140 mg/dL in patients who are eating or have NPO orders.

Eligibility criteria: Major Inclusion Criteria:

* No known history of diabetes
* Admission or pre-entry plasma glucose (PG) level between 140 and 400 mg/dL
* Non-critically ill and admitted to acute care medical services
* Have a body mass index greater than or equal to 18.5 kg/m\^2 and less than or equal to 45 kilograms per square meter (kg/m\^2)

Major Exclusion Criteria:

* Received any insulin/analog therapy for longer than 108 hours prior to study entry or intermediate- or long-acting insulin/analogs (neutral protamine Hagedorn, detemir, or glargine) in the 24 hours prior to randomization or any intravenous insulin therapy prior to randomization
* Laboratory evidence of diabetic ketoacidosis for patients with pre-randomization PG greater than 250 mg/dL
* Have taken any oral or injectable antihyperglycemic medications other than insulin within 3 months prior to study entry
* Have acute critical illness or are expected to require admission to an ICU or equivalent or be treated with glucocorticoid therapy during the hospital study period
* Expected hospitalization less than 24 hours post-randomization

Primary outcomes:
measure: Mean Plasma Glucose (MPG) Throughout Hospital Study Period
timeFrame: Throughout hospital study period (1 to 10 days post-randomization)
measure: Percentage of Capillary Plasma Glucose Measurements Within the Range of 71 to 179 mg/dL Throughout the Hospital Study Period
timeFrame: Throughout hospital study period (1 to 10 days post-randomization)
Secondary outcomes:
measure: Mean Plasma Glucose (MPG) by Hospital Day
timeFrame: Day 1 up to day 7 of hospital study period
measure: Percentage of Plasma Glucose Measurements Within Range 71 to 179 mg/dL by Hospital Day
timeFrame: Day 1 up to day 10 of hospital study period
measure: Percentage of Participants Achieving MPG Within Range 71 to 179 mg/dL and Within the Target of 100 to 179 mg/dL Throughout Hospital Study Period
timeFrame: Throughout hospital study period (1 to 10 days post-randomization)
measure: Percentage of Participants Achieving MPG Within Range 71 to 179 mg/dL and Within the Target of 100 to 179 mg/dL by Hospital Day
timeFrame: Day 1 up to day 10 of hospital study period
measure: Mean Fasting Plasma Glucose (FPG) by Hospital Day
timeFrame: Day 1 up to day 10 of hospital study period
measure: Mean FPG Throughout Hospital Study Period
timeFrame: Throughout hospital study period (1 to 10 days post-randomization)
measure: Percentage of Fasting Capillary PG Measurements Within the Range of 71 to 139 mg/dL and Within the Target of 100 to 139 mg/dL Throughout the Hospital Study Period
timeFrame: Throughout the hospital study period (1 to 10 days post-randomization)
measure: Percentage of Fasting Capillary PG Measurements Within the Range of 71 to 139 mg/dL and Within the Target of 100 to 139 mg/dL by Hospital Day
timeFrame: Day 1 up to day 10 of hospital study period
measure: Percentage of Participants Achieving Mean FPG Range of 71 to 139 mg/dL and Target of 100 to 139 mg/dL Throughout the Hospital Study Period
timeFrame: Throughout the hospital study period (1 to 10 days post-randomization)
measure: Percentage of Participants Achieving Mean FPG Range of 71 to 139 mg/dL and Target of 100 to 139 mg/dL by Hospital Day
timeFrame: Day 1 up to day 10 of hospital study period
measure: Percentage of Capillary PG Measurements >240 mg/dL Throughout the Hospital Study Period
timeFrame: Throughout the hospital study period (1 to 10 days post-randomization)
measure: Percentage of Capillary PG Measurements >240 mg/dL by Hospital Day
timeFrame: Day 1 up to day 10 of hospital study period
measure: Total Daily Dose (TDD) of Insulin (Units) Throughout the Hospital Study Period
timeFrame: Throughout the hospital study period (1 to 10 days post-randomization)
measure: TDD of Insulin (Units/kg) Throughout the Hospital Study Period
timeFrame: Throughout the hospital study period (1 to 10 days post-randomization)
measure: TDD of Insulin (Units) by Hospital Day
timeFrame: Day 1 up to day 10 of hospital study period
measure: TDD of Insulin (Units/kg) by Hospital Day
timeFrame: Day 1 up to day 10 of hospital study period
measure: Length of Hospital Stay Post-randomization Throughout the Hospital Study Period
timeFrame: Throughout the hospital study period (1 to 10 days post-randomization)
measure: Number (Incidence) of Hypoglycemia and Severe Hypoglycemia Episodes, Throughout Hospital Study Period
timeFrame: Throughout hospital study period (1 to 10 days post-randomization)
measure: Number of Hypoglycemia and Severe Hypoglycemia Episodes Adjusted for 30 Days (Rate), Throughout Hospital Study Period
timeFrame: Throughout hospital study period (1 to 10 days post-randomization)
measure: Number (Incidence) of Hypoglycemia and Severe Hypoglycemia Episodes, by Hospital Day
timeFrame: Day 1 up to day 10 of hospital study period
measure: Number of Hypoglycemia and Severe Hypoglycemia Episodes Adjusted for 30 Days (Rate), by Hospital Day
timeFrame: Day 1 up to day 10 of hospital study period
measure: Number of Participants With Treatment-emergent Adverse Events Throughout Hospital Study Period
timeFrame: Throughout hospital study period (1 to 10 days post-randomization)
measure: Percentage of Participants Requiring Intensive Care Unit Transfer
timeFrame: Throughout hospital study period (1 to 10 days post-randomization)
measure: Percentage of Participants With Deterioration of Renal Function Throughout the Hospital Study Period
timeFrame: Throughout hospital study period (1 to 10 days post-randomization)
measure: Percentage of Participants With Documented Nosocomial Infections
timeFrame: Throughout hospital study period (1 to 10 days post-randomization)
measure: Number of Participants With Major Adverse Cardiovascular Events (MACE)
timeFrame: Throughout hospital study period (1 to 10 days post-randomization)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Alabama
city: Jacksonville
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Florida
city: Miami
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Florida
city: Weston
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Florida
city: Atlanta
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Georgia
city: Topeka
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Kansas
city: Hazard
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Kentucky
city: Bangor
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Maine
city: Kansas City
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Missouri
city: Cleveland
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Ohio
city: Charleston
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: South Carolina
city: Memphis
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Tennessee
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Workgroup on Hypoglycemia, American Diabetes Association. Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care. 2005 May;28(5):1245-9. doi: 10.2337/diacare.28.5.1245. No abstract available.
citation: American Diabetes Association. Standards of medical care in diabetes--2010. Diabetes Care. 2010 Jan;33 Suppl 1(Suppl 1):S11-61. doi: 10.2337/dc10-S011. No abstract available.
citation: Moghissi ES, Korytkowski MT, DiNardo M, Einhorn D, Hellman R, Hirsch IB, Inzucchi SE, Ismail-Beigi F, Kirkman MS, Umpierrez GE; American Association of Clinical Endocrinologists; American Diabetes Association. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Endocr Pract. 2009 May-Jun;15(4):353-69. doi: 10.4158/EP09102.RA. No abstract available.
citation: Umpierrez GE, Smiley D, Zisman A, Prieto LM, Palacio A, Ceron M, Puig A, Mejia R. Randomized study of basal-bolus insulin therapy in the inpatient management of patients with type 2 diabetes (RABBIT 2 trial). Diabetes Care. 2007 Sep;30(9):2181-6. doi: 10.2337/dc07-0295. Epub 2007 May 18.
citation: Umpierrez GE, Hor T, Smiley D, Temponi A, Umpierrez D, Ceron M, Munoz C, Newton C, Peng L, Baldwin D. Comparison of inpatient insulin regimens with detemir plus aspart versus neutral protamine hagedorn plus regular in medical patients with type 2 diabetes. J Clin Endocrinol Metab. 2009 Feb;94(2):564-9. doi: 10.1210/jc.2008-1441. Epub 2008 Nov 18.