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

This study has been terminated.
(Low enrollment)
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01136746
First received: June 2, 2010
Last updated: November 7, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Hyperglycemia
Drug: Human regular insulin
Drug: Insulin lispro
Drug: Insulin glargine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Mean Plasma Glucose (MPG) Throughout Hospital Study Period [ Time Frame: Throughout hospital study period (1 to 10 days post-randomization) ] [ Designated as safety issue: No ]
    Overall MPG is derived as the mean of plasma glucose (PG) readings from Day/Visit 1 to Day/Visit 10.

  • Percentage of Capillary Plasma Glucose Measurements Within the Range of 71 to 179 mg/dL Throughout the Hospital Study Period [ Time Frame: Throughout hospital study period (1 to 10 days post-randomization) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Mean Plasma Glucose (MPG) by Hospital Day [ Time Frame: Day 1 up to day 7 of hospital study period ] [ Designated as safety issue: No ]
    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.

  • Percentage of Plasma Glucose Measurements Within Range 71 to 179 mg/dL by Hospital Day [ Time Frame: Day 1 up to day 10 of hospital study period ] [ Designated as safety issue: No ]
    Due to low enrollment, this outcome measure was not analyzed.

  • 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 [ Time Frame: Throughout hospital study period (1 to 10 days post-randomization) ] [ Designated as safety issue: No ]
    Due to low enrollment, this outcome measure was not analyzed.

  • 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 [ Time Frame: Day 1 up to day 10 of hospital study period ] [ Designated as safety issue: No ]
    Due to low enrollment, this outcome measure was not analyzed.

  • Mean Fasting Plasma Glucose (FPG) by Hospital Day [ Time Frame: Day 1 up to day 10 of hospital study period ] [ Designated as safety issue: No ]
    Due to low enrollment, this outcome measure was not analyzed.

  • Mean FPG Throughout Hospital Study Period [ Time Frame: Throughout hospital study period (1 to 10 days post-randomization) ] [ Designated as safety issue: No ]
    Due to low enrollment, this outcome measure was not analyzed.

  • 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 [ Time Frame: Throughout the hospital study period (1 to 10 days post-randomization) ] [ Designated as safety issue: No ]
    Due to low enrollment, this outcome measure was not analyzed.

  • 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 [ Time Frame: Day 1 up to day 10 of hospital study period ] [ Designated as safety issue: No ]
    Due to low enrollment, this outcome measure was not analyzed.

  • 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 [ Time Frame: Throughout the hospital study period (1 to 10 days post-randomization) ] [ Designated as safety issue: No ]
    Due to low enrollment, this outcome measure was not analyzed.

  • Percentage of Participants Achieving Mean FPG Range of 71 to 139 mg/dL and Target of 100 to 139 mg/dL by Hospital Day [ Time Frame: Day 1 up to day 10 of hospital study period ] [ Designated as safety issue: No ]
    Due to low enrollment, this outcome measure was not analyzed.

  • Percentage of Capillary PG Measurements >240 mg/dL Throughout the Hospital Study Period [ Time Frame: Throughout the hospital study period (1 to 10 days post-randomization) ] [ Designated as safety issue: No ]
    Due to low enrollment, this outcome measure was not analyzed.

  • Percentage of Capillary PG Measurements >240 mg/dL by Hospital Day [ Time Frame: Day 1 up to day 10 of hospital study period ] [ Designated as safety issue: No ]
    Due to low enrollment, this outcome measure was not analyzed.

  • Total Daily Dose (TDD) of Insulin (Units) Throughout the Hospital Study Period [ Time Frame: Throughout the hospital study period (1 to 10 days post-randomization) ] [ Designated as safety issue: No ]
    Due to low enrollment, this outcome measure was not analyzed.

  • TDD of Insulin (Units/kg) Throughout the Hospital Study Period [ Time Frame: Throughout the hospital study period (1 to 10 days post-randomization) ] [ Designated as safety issue: No ]
    Due to low enrollment, this outcome measure was not analyzed.

  • TDD of Insulin (Units) by Hospital Day [ Time Frame: Day 1 up to day 10 of hospital study period ] [ Designated as safety issue: No ]
    Due to low enrollment, this outcome measure was not analyzed.

  • TDD of Insulin (Units/kg) by Hospital Day [ Time Frame: Day 1 up to day 10 of hospital study period ] [ Designated as safety issue: No ]
    Due to low enrollment, this outcome measure was not analyzed.

  • Length of Hospital Stay Post-randomization Throughout the Hospital Study Period [ Time Frame: Throughout the hospital study period (1 to 10 days post-randomization) ] [ Designated as safety issue: No ]
    Due to low enrollment, this outcome measure was not analyzed.

  • Number (Incidence) of Hypoglycemia and Severe Hypoglycemia Episodes, Throughout Hospital Study Period [ Time Frame: Throughout hospital study period (1 to 10 days post-randomization) ] [ Designated as safety issue: Yes ]
    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.

  • Number of Hypoglycemia and Severe Hypoglycemia Episodes Adjusted for 30 Days (Rate), Throughout Hospital Study Period [ Time Frame: Throughout hospital study period (1 to 10 days post-randomization) ] [ Designated as safety issue: No ]
    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.

  • Number (Incidence) of Hypoglycemia and Severe Hypoglycemia Episodes, by Hospital Day [ Time Frame: Day 1 up to day 10 of hospital study period ] [ Designated as safety issue: No ]
    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.

  • Number of Hypoglycemia and Severe Hypoglycemia Episodes Adjusted for 30 Days (Rate), by Hospital Day [ Time Frame: Day 1 up to day 10 of hospital study period ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Treatment-emergent Adverse Events Throughout Hospital Study Period [ Time Frame: Throughout hospital study period (1 to 10 days post-randomization) ] [ Designated as safety issue: Yes ]
    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.

  • Percentage of Participants Requiring Intensive Care Unit Transfer [ Time Frame: Throughout hospital study period (1 to 10 days post-randomization) ] [ Designated as safety issue: No ]
    Due to low enrollment, this outcome measure was not analyzed.

  • Percentage of Participants With Deterioration of Renal Function Throughout the Hospital Study Period [ Time Frame: Throughout hospital study period (1 to 10 days post-randomization) ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Documented Nosocomial Infections [ Time Frame: Throughout hospital study period (1 to 10 days post-randomization) ] [ Designated as safety issue: No ]
    Due to low enrollment, this outcome measure was not analyzed.

  • Number of Participants With Major Adverse Cardiovascular Events (MACE) [ Time Frame: Throughout hospital study period (1 to 10 days post-randomization) ] [ Designated as safety issue: No ]
    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.


Enrollment: 16
Study Start Date: March 2011
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Sliding scale regular insulin Drug: Human regular insulin
Administered subcutaneously, four times daily, according to sliding scale insulin algorithm throughout hospital study period (1 to 10 days post-randomization)
Other Names:
  • Humulin R
  • LY041001
Experimental: Basal-bolus therapy Drug: Insulin lispro
Administered subcutaneously, 3 to 4 times daily, according to plasma glucose levels throughout hospital study period (1 to 10 days post-randomization)
Other Names:
  • Humalog
  • LY275585
Drug: Insulin glargine
Administered subcutaneously, once daily, according to plasma glucose levels throughout hospital study period (1 to 10 days post-randomization)
Other Name: Lantus

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01136746

Locations
United States, Alabama
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.
Birmingham, Alabama, United States, 35294
United States, Florida
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.
Jacksonville, Florida, United States, 32209
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.
Miami, Florida, United States, 33136
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.
Weston, Florida, United States, 33331
United States, Georgia
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.
Atlanta, Georgia, United States, 30312
United States, Kansas
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.
Topeka, Kansas, United States, 66604
United States, Kentucky
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.
Hazard, Kentucky, United States, 41701
United States, Maine
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.
Bangor, Maine, United States, 04401
United States, Missouri
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.
Kansas City, Missouri, United States, 64111
United States, Ohio
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.
Cleveland, Ohio, United States, 44106
United States, South Carolina
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.
Charleston, South Carolina, United States, 29425
United States, Tennessee
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.
Memphis, Tennessee, United States, 38104
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: 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) Eli Lilly and Company
  More Information

Publications:
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01136746     History of Changes
Other Study ID Numbers: 13698, F3Z-US-IOPZ
Study First Received: June 2, 2010
Results First Received: September 12, 2012
Last Updated: November 7, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Hyperglycemia
Diabetes
Hospital
Diabetic

Additional relevant MeSH terms:
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Insulin, Globin Zinc
Glargine
Insulin
Insulin Lispro
Insulin, Long-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014