Hospital Management of Hyperglycemia Study of Insulin Glargine Plus Insulin Lispro Versus Human Regular Insulin

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Hyperglycemia

Intervention / Treatment
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* Drug: Human regular insulin
* Drug: Insulin lispro
* Drug: Insulin glargine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sliding scale regular insulin<br> | Drug: Human regular insulin<br>* Administered subcutaneously, four times daily, according to sliding scale insulin algorithm throughout hospital study period (1 to 10 days post-randomization)<br>* Other names: LY041001;|
| Experimental: Basal-bolus therapy<br> | Drug: Insulin lispro<br>* Administered subcutaneously, 3 to 4 times daily, according to plasma glucose levels throughout hospital study period (1 to 10 days post-randomization)<br>* Other names: LY275585;Drug: Insulin glargine<br>* Administered subcutaneously, once daily, according to plasma glucose levels throughout hospital study period (1 to 10 days post-randomization)<br>* Other names: Lantus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Plasma Glucose (MPG) Throughout Hospital Study Period | Overall MPG is derived as the mean of plasma glucose (PG) readings from Day/Visit 1 to Day/Visit 10. | Throughout hospital study period (1 to 10 days post-randomization) | 
| Percentage of Capillary Plasma Glucose Measurements Within the Range of 71 to 179 mg/dL Throughout the Hospital Study Period | Results are reported as the percentage of total number of capillary plasma glucose measurements within the range of 71 to 179 mg/dL for each treatment arm. | Throughout hospital study period (1 to 10 days post-randomization) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Plasma Glucose (MPG) by Hospital Day | The intent was to report results up to Day 10; however, due to low enrollment, mean and standard deviations are only reported up to Day 7. | Day 1 up to day 7 of hospital study period | 
| Percentage of Plasma Glucose Measurements Within Range 71 to 179 mg/dL by Hospital Day | Due to low enrollment, this outcome measure was not analyzed. | Day 1 up to day 10 of hospital study period | 
| 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 | Due to low enrollment, this outcome measure was not analyzed. | Throughout hospital study period (1 to 10 days post-randomization) | 
| 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 | Due to low enrollment, this outcome measure was not analyzed. | Day 1 up to day 10 of hospital study period | 
| Mean Fasting Plasma Glucose (FPG) by Hospital Day | Due to low enrollment, this outcome measure was not analyzed. | Day 1 up to day 10 of hospital study period | 
| Mean FPG Throughout Hospital Study Period | Due to low enrollment, this outcome measure was not analyzed. | Throughout hospital study period (1 to 10 days post-randomization) | 
| 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 | Due to low enrollment, this outcome measure was not analyzed. | Throughout the hospital study period (1 to 10 days post-randomization) | 
| 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 | Due to low enrollment, this outcome measure was not analyzed. | Day 1 up to day 10 of hospital study period | 
| 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 | Due to low enrollment, this outcome measure was not analyzed. | Throughout the hospital study period (1 to 10 days post-randomization) | 
| Percentage of Participants Achieving Mean FPG Range of 71 to 139 mg/dL and Target of 100 to 139 mg/dL by Hospital Day | Due to low enrollment, this outcome measure was not analyzed. | Day 1 up to day 10 of hospital study period | 
| Percentage of Capillary PG Measurements >240 mg/dL Throughout the Hospital Study Period | Due to low enrollment, this outcome measure was not analyzed. | Throughout the hospital study period (1 to 10 days post-randomization) | 
| Percentage of Capillary PG Measurements >240 mg/dL by Hospital Day | Due to low enrollment, this outcome measure was not analyzed. | Day 1 up to day 10 of hospital study period | 
| Total Daily Dose (TDD) of Insulin (Units) Throughout the Hospital Study Period | Due to low enrollment, this outcome measure was not analyzed. | Throughout the hospital study period (1 to 10 days post-randomization) | 
| TDD of Insulin (Units/kg) Throughout the Hospital Study Period | Due to low enrollment, this outcome measure was not analyzed. | Throughout the hospital study period (1 to 10 days post-randomization) | 
| TDD of Insulin (Units) by Hospital Day | Due to low enrollment, this outcome measure was not analyzed. | Day 1 up to day 10 of hospital study period | 
| TDD of Insulin (Units/kg) by Hospital Day | Due to low enrollment, this outcome measure was not analyzed. | Day 1 up to day 10 of hospital study period | 
| Length of Hospital Stay Post-randomization Throughout the Hospital Study Period | Due to low enrollment, this outcome measure was not analyzed. | Throughout the hospital study period (1 to 10 days post-randomization) | 
| Number (Incidence) of Hypoglycemia and Severe Hypoglycemia Episodes, Throughout Hospital Study Period | Hypoglycemia was defined as any time a recorded capillary PG level is ≤70 mg/dL, even if it is not associated with signs or symptoms, or treatment consistent with current guidelines (ADA 2005; ADA 2010). Severe hypoglycemia was defined as an episode associated with a recorded capillary (or venous) PG <40 mg/dL (Umpierrez et al. 2007; Moghissi et al. 2009; Umpierrez et al. 2009), even if it is not associated with need for assistance or neuroglycopenic symptoms (ADA 2005) or prompt recovery after oral carbohydrate, glucagon, or IV glucose. | Throughout hospital study period (1 to 10 days post-randomization) | 
| Number of Hypoglycemia and Severe Hypoglycemia Episodes Adjusted for 30 Days (Rate), Throughout Hospital Study Period | Hypoglycemia was defined as any time a recorded capillary PG level is ≤70 mg/dL, even if it is not associated with signs or symptoms, or treatment consistent with current guidelines (ADA 2005; ADA 2010). Severe hypoglycemia was defined as an episode associated with a recorded capillary (or venous) PG <40 mg/dL, even if it is not associated with need for assistance or neuroglycopenic symptoms (ADA 2005) or prompt recovery after oral carbohydrate, glucagon, or IV glucose. Due to low enrollment, this outcome measure was not analyzed. | Throughout hospital study period (1 to 10 days post-randomization) | 
| Number (Incidence) of Hypoglycemia and Severe Hypoglycemia Episodes, by Hospital Day | Hypoglycemia was defined as any time a recorded capillary PG level is ≤70 mg/dL, even if it is not associated with signs or symptoms, or treatment consistent with current guidelines (ADA 2005; ADA 2010). Severe hypoglycemia was defined as an episode associated with a recorded capillary (or venous) PG <40 mg/dL, even if it is not associated with need for assistance or neuroglycopenic symptoms (ADA 2005) or prompt recovery after oral carbohydrate, glucagon, or IV glucose. Due to low enrollment, this outcome measure was not analyzed. | Day 1 up to day 10 of hospital study period | 
| Number of Hypoglycemia and Severe Hypoglycemia Episodes Adjusted for 30 Days (Rate), by Hospital Day | Hypoglycemia was defined as any time a recorded capillary PG level is ≤70 mg/dL, even if it is not associated with signs or symptoms, or treatment consistent with current guidelines (ADA 2005; ADA 2010). Severe hypoglycemia was defined as an episode associated with a recorded capillary (or venous) PG <40 mg/dL, even if it is not associated with need for assistance or neuroglycopenic symptoms (ADA 2005) or prompt recovery after oral carbohydrate, glucagon, or IV glucose. Due to low enrollment, this outcome measure was not analyzed. | Day 1 up to day 10 of hospital study period | 
| Number of Participants With Treatment-emergent Adverse Events Throughout Hospital Study Period | Treatment-emergent adverse event - any untoward medical occurrence that either occurred or worsened at any time after treatment baseline and which did not necessarily have a causal relationship with this treatment. A summary of adverse events is located in the Reported Adverse Event Module. | Throughout hospital study period (1 to 10 days post-randomization) | 
| Percentage of Participants Requiring Intensive Care Unit Transfer | Due to low enrollment, this outcome measure was not analyzed. | Throughout hospital study period (1 to 10 days post-randomization) | 
| Percentage of Participants With Deterioration of Renal Function Throughout the Hospital Study Period | Deterioration of renal function was defined by an increase in serum creatinine by >0.5 milligrams per deciliter (mg/dL). Due to low enrollment, this outcome measure was not analyzed. | Throughout hospital study period (1 to 10 days post-randomization) | 
| Percentage of Participants With Documented Nosocomial Infections | Due to low enrollment, this outcome measure was not analyzed. | Throughout hospital study period (1 to 10 days post-randomization) | 
| Number of Participants With Major Adverse Cardiovascular Events (MACE) | MACE was defined as the composite of all-cause death, nonfatal myocardial infarction (MI), or nonfatal stroke. Due to low enrollment, this outcome measure was not analyzed. | Throughout hospital study period (1 to 10 days post-randomization) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperglycemia, Diabetes, Hospital, Diabetic