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A Trial Comparing Insulin Degludec and Glargine U100 for Management of Hospitalized and Discharged Patients With Type 2 Diabetes

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ClinicalTrials.gov Identifier: NCT03336528
Recruitment Status : Recruiting
First Posted : November 8, 2017
Last Update Posted : October 3, 2018
Sponsor:
Collaborator:
Novo Nordisk A/S
Information provided by (Responsible Party):
Guillermo Umpierrez, MD, Emory University

Brief Summary:
The purpose of this study is to find out if treatment with Degludec insulin when compared to glargine U100 insulin will result in similar blood sugar control in patients with diabetes, who are admitted to the hospital and then transition at home, after discharge from the hospital.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Drug: Degludec Drug: Glargine Drug: Aspart Drug: Degludec post-discharge Drug: Glargine U100 post-discharge Phase 4

Detailed Description:
Several outpatient trials have reported that treatment with degludec results in comparable improvement in HbA1c levels and in lower rates of hypoglycemia compared to glargine U100 insulin. However, no previous studies have compared the safety and efficacy of the long-acting basal insulin degludec in the inpatient management of patients with diabetes. It is expected that a large number of patients with diabetes will be started or transitioned to this new insulin formulation; so acquiring knowledge on their safety and efficacy is of great clinical interest. Accordingly, the proposed study will provide novel and clinically useful information on the efficacy (blood glucose control) and safety (hypoglycemia) of degludec in the inpatient setting and after hospital discharge in general medicine and surgery patients with Type 2 Diabetes (T2D).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Degludec-Glargine Hospital Trial: A Randomized Controlled Trial Comparing Insulin and Glargine U100 for the Inpatient and Post-Hospital Discharge Management of Medicine and Surgery Patients With Type 2 Diabetes
Actual Study Start Date : January 2, 2018
Estimated Primary Completion Date : June 30, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Degludec inpatient
Study participants treated with insulin prior to admission will receive 80% of the total daily dose (TDD) given as a basal bolus regimen with degludec once daily plus rapid-acting aspart insulin before meals. Degludec insulin 100 Units/mL, average dose: 30-45 U/day. aspart (U-100) insulin 100 Units/mL, average dose: 20-30 U/day.
Drug: Degludec
Degludec is a long-acting human insulin analog indicated to improve glycemic control in adults with diabetes mellitus. Patients will be treated with bolus regimen given half of total daily dose (TDD) as basal once daily and half as aspart divided in three equal doses before meals. Patients with poor oral intake or with medical instruction to withhold oral intake (NPO) will receive the basal dose, but prandial dose will be held. Insulin dose will be adjusted daily to maintain a fasting and pre-dinner BG between 100 mg/dl and 180 mg/dl.
Other Name: Tresiba

Drug: Aspart
Aspart insulin will be given in three equally divided doses before each meal. To prevent hypoglycemia, if a subject is not able to eat, aspart insulin dose will be held.
Other Name: Novolog

Active Comparator: Glargine U100 inpatient

Study participants treated with insulin prior to admission will receive 80% of the total daily dose (TDD) given as basal bolus regimen with glargine once daily plus rapid-acting aspart insulin before meals. Glargine (U-100) insulin 100 Units/mL, average dose: 30-45 U/day.

Aspart (U-100) insulin 100 Units/mL, average dose: 20-30 U/day.

Drug: Glargine
Glargine is a long-acting human insulin analog indicated to improve glycemic control in adults with diabetes mellitus. Patients will be treated with bolus regimen given half of total daily dose (TDD) as basal once daily and half as aspart divided in three equal doses before meals. Patients with poor oral intake or with medical instruction to withhold oral intake (NPO) will receive the basal dose, but prandial dose will be held. Insulin dose will be adjusted daily to maintain a fasting and pre-dinner BG between 100 mg/dl and 180 mg/dl.
Other Name: Lantus

Drug: Aspart
Aspart insulin will be given in three equally divided doses before each meal. To prevent hypoglycemia, if a subject is not able to eat, aspart insulin dose will be held.
Other Name: Novolog

Experimental: Degludec post-discharge
Patients with poorly controlled diabetes (HbA1c >7.5%) enrolled in the degludec inpatient arm will be invited to participate in the prospective outpatient study. At hospital discharge, patients will be treated following an HbA1c based algorithm for a total duration of the outpatient follow-up of 3 months. Patients with an HbA1c between 7.5% and 10% will be discharged on preadmission oral antidiabetic agents plus degludec once daily. Patients with an admission A1C ≥ 10% will be discharged on basal bolus regimen with degludec and aspart insulin before meals.
Drug: Aspart
Aspart insulin will be given in three equally divided doses before each meal. To prevent hypoglycemia, if a subject is not able to eat, aspart insulin dose will be held.
Other Name: Novolog

Drug: Degludec post-discharge
Patients with an HbA1c between 7.5% and 10% will be discharged on preadmission oral antidiabetic agents plus degludec once daily. Patients with an admission A1C ≥ 10% will be discharged on basal bolus regimen with degludec and aspart insulin before meals.
Other Name: Tresiba

Active Comparator: Glargine U100 post-discharge
Patients with poorly controlled diabetes (HbA1c >7.5%) enrolled in glargine inpatient arm will be invited to participate in this open label prospective outpatient study. At hospital discharge, patients will be treated following an HbA1c based algorithm for a total duration of the outpatient follow-up of 3 months. Patients with an HbA1c between 7.5% and 10% will be discharged on preadmission oral antidiabetic agents plus glargine once daily. Patients with an admission A1C ≥ 10% will be discharged on basal bolus regimen with glargine and aspart insulin before meals.
Drug: Aspart
Aspart insulin will be given in three equally divided doses before each meal. To prevent hypoglycemia, if a subject is not able to eat, aspart insulin dose will be held.
Other Name: Novolog

Drug: Glargine U100 post-discharge
Patients with an admission A1C ≥ 10% will be discharged on basal bolus regimen with glargine and aspart insulin before meals.
Other Name: Lantus




Primary Outcome Measures :
  1. Change in mean daily blood glucose concentration in hospitalized patients. [ Time Frame: Baseline, up to the first 10 days of therapy ]
    Blood glucose will be measured before each meal and at bedtime. Mean daily blood glucose concentration will be calculated to determine differences in inpatient glycemic control in general medicine and surgery patients with Type 2 Diabetes (T2D) treated with basal bolus regimen with insulin degludec or glargine once daily plus aspart insulin before meals.

  2. Change in mean daily blood glucose concentration in discharged patients. [ Time Frame: Day 11 (day of discharge), Up to 12 weeks after hospital discharge ]
    Blood glucose will be measured before each meal and at bedtime. Mean daily blood glucose concentration will be calculated to determine differences in outpatient glycemic control in patients with Type 2 Diabetes (T2D) treated with basal bolus regimen with insulin degludec or glargine once daily plus aspart insulin before meals. Information will be collected via bi-weekly phone interviews and during 4- and 12- weeks outpatient study visits.


Secondary Outcome Measures :
  1. Levels Hemoglobin A1c (HbA1c) in discharged patients [ Time Frame: 4 weeks after hospital discharge,12 weeks after hospital discharge ]
    The HbA1C test reflects the average of a person's blood glucose levels over the past 3 months.

  2. Number of basic glucose (BG) readings between 70 mg/dl and 180 mg/dl before meals in hospitalized patients. [ Time Frame: The first 10 days of therapy ]
    Blood glucose will be measured before each meal and at bedtime, and proportion of basic glucose (BG) readings between 70 mg/dl and 180 mg/dl will be recorded.

  3. Number of basic glucose (BG) readings between 70 mg/dl and 180 mg/dl before meals in discharged patients [ Time Frame: Up to 12 weeks after hospital discharge ]
    Blood glucose will be measured before each meal and at bedtime, and proportion of basic glucose (BG) readings between 70 mg/dl and 180 mg/dl will be recorded. Information will be collected via bi-weekly phone interviews and during 4- and 12- weeks outpatient study visits.

  4. Number of hypoglycemic episodes (BG < 70 mg/dl and 54 mg/dl) in hospitalized patients [ Time Frame: The first 10 days of therapy ]
    Blood glucose will be measured before each meal and at bedtime, and number of hypoglycemic episodes (< 70 mg/dl and 54 mg/dl) will be recorded.

  5. Number of hypoglycemia (< 70 mg/dl and 54 mg/dl) episodes in discharged patients [ Time Frame: Up to 12 weeks after hospital discharge ]
    Blood glucose will be measured before each meal and at bedtime. and number of hypoglycemia (< 70 mg/dl and 54 mg/dl) episodes will be recorded via bi-weekly phone interviews and during 4- and 12- weeks outpatient study visits.

  6. Number of severe hypoglycemia (< 54 mg/dl) episodes in hospitalized patients [ Time Frame: The first 10 days of therapy ]
    Blood glucose will be measured before each meal and at bedtime, and number of hypoglycemia (BG< 54 mg/dl) episodes will be recorded.

  7. Number of severe hypoglycemia (BG< 54 mg/dl) episodes in discharged patients [ Time Frame: Up to 12 weeks after hospital discharge ]
    Blood glucose will be measured before each meal and at bedtime, and number of episodes of severe hypoglycemia (BG< 54 mg/dl) episodes will be recorded.

  8. Number of episodes of severe hyperglycemia (BG > 240 mg/dl) in hospitalized patients [ Time Frame: The first 10 days of therapy ]
    Blood glucose will be measured before each meal and at bedtime, and number of severe hyperglycemia (BG > 240 mg/dl) episodes will be recorded

  9. Number of episodes of severe hyperglycemia (BG > 240 mg/dl) in discharged patients [ Time Frame: Up to 12 weeks after hospital discharge ]
    Blood glucose will be measured before each meal and at bedtime, and number of severe hyperglycemia (BG > 240 mg/dl) episodes will be recorded.

  10. Daily dose of basal insulin, daily dose of prandial insulin, and total daily dose in hospitalized patients [ Time Frame: The first 10 days of therapy ]
    Electronic medical records and nursing records will be used to document day and time of insulin administration of study drug given once daily and prandial- rapid-acting insulin (aspart) given before meals. The study team will also record dose and number of units given as supplement (correction) to correct hyperglycemia.

  11. Daily dose of basal insulin, daily dose of prandial insulin, and total daily dose in discharged patients [ Time Frame: Up to 12 weeks after hospital discharge ]
    Patients will be contacted every 2 weeks after discharge by a study coordinator to assess insulin administration, glycemic control, hypoglycemia and medication adherence. Patients are to bring all used and unused insulin pens (study drug). Patients will keep daily record of time and dose of insulin administered every day during the study period.


Other Outcome Measures:
  1. Number of re-admissions (hospitalization) and Emergency room visits [ Time Frame: Up to 12 weeks after hospital discharge ]
    The number of re-admissions (hospitalizations) and Emergency Room visits will be recorded.

  2. Number of cardiac complications in hospitalized patients [ Time Frame: Up to the time of discharge (an expected average of 10 days) ]
    Cardiac complications are defined as myocardial infarction, cardiac arrhythmia requiring medical treatment, or cardiac arrest. The number of cardiac complications in hospitalized patients will be recorded.

  3. Number of cardiac complications in discharged patients [ Time Frame: Up to 12 weeks after hospital discharge ]
    Cardiac complications are defined as myocardial infarction, cardiac arrhythmia requiring medical treatment, or cardiac arrest. Number of cardiac complications in discharged patients will be recorded.

  4. Number of acute kidney injury in hospitalized patients [ Time Frame: Up to the time of discharge (an expected average of 10 days) ]
    Acute kidney injury defined as an increment in serum creatinine ≥ 0.3 mg/dL from baseline or ≥1.5 times baseline creatinine (KDIGO).Number of acute kidney injury in hospitalized patients. Number of acute kidney injury in hospitalized patients will be recorded.

  5. Number of acute kidney injury in discharged patients [ Time Frame: Up to 12 weeks after hospital discharge ]
    Acute kidney injury defined as an increment in serum creatinine ≥ 0.3 mg/dL from baseline or ≥1.5 times baseline creatinine (KDIGO). Number of acute kidney injury in discharged patients will be recorded.

  6. Length of hospital stay [ Time Frame: Up to 10 days (expected average) ]
    The number of days of hospital stay will be recorded.

  7. Hospital mortality [ Time Frame: During hospital stay ( expected average of up to 10 days) ]
    Number of deaths in the study hospitalized patients will be recorded and death rate will be calculated.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males or females between > 18 years admitted to a general medicine or surgical service.
  2. A known history of T2D treated either with diet alone, oral monotherapy, any combination of oral antidiabetic agents, short-acting GLP1-RA (exenatide, liraglutide) or insulin therapy except for degludec and glargine U300.
  3. Medical and surgical patients expected to be admitted length of stay (LOS) longer than 3 days
  4. Subjects must have a randomization BG > 140 mg and < 400 mg/dL without laboratory evidence of diabetic ketoacidosis (bicarbonate < 18 mEq/L, pH < 7.30, or positive serum or urinary ketones).
  5. Signed, informed consent and HIPAA documentation prior to any study procedures

Exclusion Criteria:

  1. Subjects with increased BG concentration, but without a known history of diabetes (stress hyperglycemia).
  2. Subjects treated with diet alone (no antidiabetic agents) and admission HbA1c <7%.
  3. Subjects with a history of diabetic ketoacidosis and hyperosmolar hyperglycemic state, or ketonuria 32.
  4. Patients treated with degludec or glargine U300, or with long-acting weekly GLP1-RA (weekly exenatide, dulaglutide or albiglutide).
  5. Patients with acute critical or surgical illness admitted to the ICU or expected to require admission to the ICU.
  6. Patients with history of clinically relevant hepatic disease (diagnosed liver cirrhosis and portal hypertension), ongoing corticosteroid therapy (equal to a prednisone dose ≥5 mg/day), or impaired renal function (eGFR< 30 ml/min), or congestive heart failure (NYHA- IV).
  7. Patients with medical and surgical pancreatic disease.
  8. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study.
  9. Female subjects who are pregnant or breast feeding at time of enrollment into the study.
  10. Known or suspected allergy to trial medication(s), excipients, or related products.
  11. Previous participation in this trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03336528


Contacts
Contact: Guillermo Umpierrez 404-778-1665 geumpie@emory.edu
Contact: Saumeth Cardona Bolivar, MD 404-616-4827 scardon@emory.edu

Locations
United States, Georgia
Grady Hospital Recruiting
Atlanta, Georgia, United States, 30308
Contact: Guillermo Umpierrez, MD    404-778-1665    geumpie@emory.edu   
Emory University Hospital Clinical Research Network Recruiting
Atlanta, Georgia, United States, 30322
Contact: Guillermo Umpierrez, MD    404-778-1665    geumpie@emory.edu   
United States, New York
Mount Sinai Recruiting
New York, New York, United States, 10029
Contact: David W Lam, MD       david.w.lam@mssm.edu   
Principal Investigator: David W Lam, MD         
Sponsors and Collaborators
Emory University
Novo Nordisk A/S
Investigators
Principal Investigator: Guillermo Umpierrez, MD Emory University

Responsible Party: Guillermo Umpierrez, MD, Professor, Emory University
ClinicalTrials.gov Identifier: NCT03336528     History of Changes
Other Study ID Numbers: IRB00087816
First Posted: November 8, 2017    Key Record Dates
Last Update Posted: October 3, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Guillermo Umpierrez, MD, Emory University:
Long-acting insulin analog

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hypoglycemic Agents
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Insulin
Insulin Glargine
Insulin Aspart
Insulin, Long-Acting
Physiological Effects of Drugs