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Sitagliptin in Non-Diabetic Patients Undergoing Cardiac Surgery (SITACABG NonDM)

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ClinicalTrials.gov Identifier: NCT02443402
Recruitment Status : Completed
First Posted : May 13, 2015
Results First Posted : February 6, 2018
Last Update Posted : February 6, 2018
Sponsor:
Information provided by (Responsible Party):
Guillermo Umpierrez, Emory University

Tracking Information
First Submitted Date  ICMJE May 11, 2015
First Posted Date  ICMJE May 13, 2015
Results First Submitted Date  ICMJE December 1, 2017
Results First Posted Date  ICMJE February 6, 2018
Last Update Posted Date February 6, 2018
Study Start Date  ICMJE January 2016
Actual Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 8, 2018)
  • Number of Participants With Stress Hyperglycemic Events in the Intensive Care Unit (ICU) [ Time Frame: Post-Surgery (Up to 4 Days) ]
    Number of participants who developed stress hyperglycemia (BG >180 mg/dl) during coronary artery bypass grafting (CABG) or after CABG requiring continuous IV insulin infusion (CII) while in the ICU.
  • Number of Subjects With Persistent Hyperglycemia [ Time Frame: Post-Surgery (Up to 10 Days) ]
    Number of subjects with persistent hyperglycemia (2 consecutive fasting and/or premeal BG > 180 mg/dL, or with average daily BG >180 mg/dl) who require insulin glargine (rescue therapy) after discontinuation of continuous intravenous insulin (CII)
Original Primary Outcome Measures  ICMJE
 (submitted: May 11, 2015)
  • Frequency of stress hyperglycemia in the intensive care unit (ICU) [ Time Frame: 2 days (average time of discharge from ICU) ]
    Number of hyperglycemic events (BG >160 mg/dl) in the ICU
  • Number of Subjects With Persistent Hyperglycemia [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Number of subjects with persistent hyperglycemia (2 consecutive fasting and/or premeal BG > 180 mg/dL, or with average daily BG >180 mg/dl) who require insulin glargine (rescue therapy) after discontinuation of continuous intravenous insulin (CII)
Change History Complete list of historical versions of study NCT02443402 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 8, 2018)
  • Need for Continuous Intravenous Insulin (CII) for Treatment of Hyperglycemia [ Time Frame: Post-Surgery (Up to 4 Days) ]
    Number of subjects with hyperglycemia (BG >180 mg/dL) who require CII in the ICU.
  • Mean Daily Intensive Care Unit (ICU) Blood Glucose (BG) Concentration [ Time Frame: Post-Surgery (Up to 4 Days) ]
    The blood glucose levels will be assessed throughout the day using a glucose meter. An average will be calculated. The normal BG range for someone with diabetes is 80-130 mg/dL.
  • Mean Amount of Insulin Therapy in the Intensive Care Unit (ICU) [ Time Frame: Post-Surgery (Up to 4 Days) ]
    The mean number of insulin infusions given per day (unit/day) while subjects are in the ICU. The more insulin given, the more hyperglycemic events experienced.
  • Duration of Continuous Intravenous Insulin (CII) [ Time Frame: Post-Intensive Care Unit (ICU) Discharge (Up to 4 Days) ]
    Mean number of hours on continuous intravenous insulin (CII) after ICU discharge.
  • Mean Units Subcutaneous (SQ) Insulin Required [ Time Frame: Post-Surgery (Up to 10 Days) ]
    Mean number of supplemental insulin units (lispro or aspart) administered after receiving insulin glargine (SQ insulin).
  • Mean Blood Glucose (BG) Concentration After Transition From Intensive Care Unit (ICU) [ Time Frame: Post-Surgery (Up to 4 Days) ]
    The blood glucose levels will be assessed throughout the day using a glucose meter after transition form the ICU. The normal BG range for someone with diabetes is 80-130 mg/dL.
  • Total Insulin Therapy in the Intensive Care Unit (ICU) [ Time Frame: Post-Surgery (Up to 4 Days) ]
    Total amount of insulin glargine insulin (units) administered in the ICU per day.
  • Number of Participants With Severe Hyperglycemic Events During Continuous Insulin Infusion (CII) [ Time Frame: Post-Surgery (Up to 4 Days) ]
    Number of participants with two consecutive blood glucose concentrations >180 mg/dL in ICU during CII.
  • Number of Participants With Hyperglycemia After Transition From Intensive Care Unit (ICU) [ Time Frame: Post-Surgery (Up to 10 Days) ]
    Number of participants with blood glucose (BG) >180 after transition from ICU.
  • Number of Participants With Hypoglycemia During Intensive Care Unit (ICU) Stay [ Time Frame: Post-Surgery (Up to 4 Days) ]
    Number of participants with blood glucose (BG) <70 during ICU stay.
  • Number of Participants With Hypoglycemia After Transition From Intensive Care Unit (ICU) [ Time Frame: Post-Surgery (Up to 4 Days) ]
    Number of participants with blood glucose (BG) <70 after transition from ICU.
  • Number of Participants With Blood Glucose Less Than 40 mg/dl [ Time Frame: Duration of Hospitalization (Up to 30 Days) ]
    Number of participants with blood glucose (BG) <40 throughout the duration of hospitalization.
  • Hospital Mortality Rate [ Time Frame: Post-Surgery (Up to 10 Days) ]
    The total number of subject deaths during hospital stay will be recorded.
  • Intensive Care Unit (ICU) Mortality Rate [ Time Frame: Post-Surgery (Up to 4 Days) ]
    The total number of subject deaths during ICU stay will be recorded.
  • Number of Participants With Cerebrovascular Events [ Time Frame: Post-Hospital Discharge (Up to 10 Days) ]
    Number of participants that experienced permanent stroke and reversible ischemic neurologic deficit events.
  • Hospital Complication Rate [ Time Frame: Duration of Hospitalization (Up to 30 days) ]
    The total number of all complications experienced during hospitalization. Participants may experience more than one complication during hospitalization and these will be included in the hospital complication rate.
  • Length of Stay: Intensive Care Unit (ICU) [ Time Frame: Post-Surgery (Up to 4 Days) ]
    Number of days in the ICU after coronary artery bypass graft surgery (CABG).
  • Length of Hospital Stay After Study Randomization [ Time Frame: Post-Randomization (Up to 9 days) ]
    Number of days in the hospital after a participant is randomized to a study intervention.
  • Number of Participants Re-admitted to the Hospital Due to Wound Infections [ Time Frame: Post-Hospital Discharge (Up to 30 Days) ]
    Number of subjects readmitted to the hospital within 30 days due to wound infection.
  • Number of Participants Re-admitted to the Hospital Not Due to Wound Infections [ Time Frame: Post-Hospital Discharge (Up to 30 Days) ]
    Number of subjects readmitted to the hospital within 30 days for all causes excluding wound infection.
  • Number of Participants With Emergency Room (ER) Visits [ Time Frame: Post-Hospital Discharge (Up to 30 Days) ]
    Number of subjects returning to the ER up to 30 days (all-cause) after hospital discharge.
  • Number of Participants With Infections Not Requiring Hospital Re-admission [ Time Frame: Post-Hospital Discharge (Up to 30 Days) ]
    Number of subjects with infections not requiring hospital re-admission within 30 days after hospital discharge.
  • Number of Subjects Requiring the Use of Inotropes for Greater Than 24 Hours [ Time Frame: Post-Surgery (Up to 2 Days) ]
    The number of subjects requiring the use of inotropes for >24 hours post CABG.
  • Number of Subjects Requiring Re-intubation [ Time Frame: Post-Surgery (Up to 2 Days) ]
    The number of subjects requiring re-intubation after CABG.
  • Number of Subjects Requiring Re-intubation Within 24 Hours [ Time Frame: Post-Surgery (Up to 24 Hours) ]
    The number of subjects requiring re-intubation with 24 after CABG.
  • Number of Subject Requiring Surgical Re-Intervention [ Time Frame: Post-Surgery (Up to 10 Days) ]
    The number of subjects that require surgical re-intervention due to mediastinal exploration and post-operative hemorrhage.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 11, 2015)
  • Need for Continuous Intravenous Insulin (CII) for Treatment of Hyperglycemia [ Time Frame: 2 days (average time of discharge from ICU) ]
    Number of subjects with hyperglycemia (BG >160 mg/dL) who require CII in the ICU
  • Mean Daily Intensive Care Unit (ICU) Blood Glucose (BG) Concentration [ Time Frame: 2 days (average time of discharge from ICU) ]
    The blood glucose levels will be assessed throughout the day using a glucose meter. An average (mean) will be calculated.
  • Mean insulin dose [ Time Frame: 2 days (average time of discharge from ICU) ]
    The insulin infusion per hour (unit/hour) and per day while subjects are in the ICU will be gathered throughout each day. An average (mean) will be calculated.
  • Duration of Continuous Intravenous Insulin (CII) [ Time Frame: 2 days (average time of discharge from ICU) ]
    Number of hours on CII
  • Number of patients requiring supplemental insulin after subcutaneous (SC) insulin [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Number of patients requiring supplemental insulin (lispro or aspart) after receiving insulin glargine (SC insulin)
  • Days of subcutaneous (SC) insulin [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Number of days subjects were on insulin glargine (SC insulin) after discontinuation of continuous intravenous insulin (CII)
  • Mean non-intensive care unit (ICU) blood glucose (BG) concentration [ Time Frame: 10 days (average time of discharge from the hospital) ]
    The blood glucose levels will be assessed throughout the day using a glucose meter. An average (mean) will be calculated.
  • Amount of insulin glargine in intensive care unit (ICU) stay [ Time Frame: 2 days (average time of discharge from ICU) ]
    Units of insulin glargine dose administered in ICU
  • Amount of insulin glargine in non-intensive care unit (ICU) stay [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Units of insulin glargine dose administered in non-ICU
  • Hyperglycemic events in intensive care unit (ICU) [ Time Frame: 2 days (average time of discharge from ICU) ]
    Number of hyperglycemic events (BG > 200 mg/dL) in ICU
  • Hyperglycemic events in non-intensive care unit (ICU) [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Number of hyperglycemic events (BG > 200 mg/dL) in non-ICU
  • Hypoglycemic events in intensive care unit (ICU) [ Time Frame: 2 days (average time of discharge from ICU) ]
    Number of hypoglycemic events (BG ≤ 70 mg/dL) in ICU
  • Hypoglycemic events in non-intensive care unit (ICU) [ Time Frame: 2 days (average time of discharge from ICU) ]
    Number of hypoglycemic events (BG ≤ 70 mg/dL) in non-ICU
  • Severe hypoglycemic events in intensive care unit (ICU) [ Time Frame: 2 days (average time of discharge from ICU) ]
    Number of severe hypoglycemic events (BG ≤ 40 mg/dL) in ICU
  • Severe hypoglycemic events in non-intensive care unit (ICU) [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Number of severe hypoglycemic events (BG ≤ 40 mg/dL) in non-ICU
  • Hospital Mortality [ Time Frame: 10 days (average time of discharge from the hospital) ]
    The total number of subject deaths during hospital stay will be recorded.
  • ICU Mortality [ Time Frame: 2 days (average time of discharge from the ICU) ]
    The total number of subject deaths during ICU stay will be recorded.
  • Number of subjects that experienced hospital complications [ Time Frame: 10 days (average time of discharge from the hospital) ]
    The total number of subjects in which hospital complications occurred prior to discharge will be recorded. These complications will include sternal wound infection (deep and superficial), bacteremia, pneumonia, acute renal failure, and acute myocardial infarction.
  • Duration of ventilator support [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Number of days on ventilator support
  • Length of intensive care unit (ICU) stay [ Time Frame: 2 days (average time of discharge from ICU) ]
    Number of days in the ICU
  • Length of hospital stay [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Number of days in the hospital
  • ICU readmissions [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Number of readmissions to intensive care unit during the same hospital course
  • Cerebrovascular events [ Time Frame: 10 days (average time of discharge from the hospital) ]
    Number of permanent stroke and reversible ischemic neurologic deficit events
  • Hospital Readmission [ Time Frame: 30 days ]
    Number of subjects readmitted to the hospital within 30 days (all-cause)
  • Emergency Room (ER) Visit [ Time Frame: 30 days ]
    Number of subjects returning to the ER within 30 days (all-cause)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sitagliptin in Non-Diabetic Patients Undergoing Cardiac Surgery
Official Title  ICMJE Sitagliptin for the Prevention and Treatment of Stress Hyperglycemia in Non-Diabetic Patients Undergoing Cardiac Surgery
Brief Summary The purpose of this study is to compare sitagliptin and placebo for the prevention of high blood glucose during surgery.
Detailed Description About 80% of patients develop high glucose after cardiac surgery. High glucose is linked to an increased risk of hospital complications. High glucose increases the risk of wound infection, kidney failure and death. Patients with high glucose are treated with insulin given through an arm vein or by frequent insulin injections under the skin. This study will determine if sitagliptin can prevent the development of high glucose after heart surgery. Sitagliptin is a diabetes pill approved by the Food and Drug Administration (FDA) to treat patients with diabetes.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE Coronary Artery Disease
Intervention  ICMJE
  • Drug: Sitagliptin
    Subjects will take one pill daily until the day prior to them being discharged from the hospital. Sitagliptin will be dispensed orally at 100 mg/day and at a lower dose 50 mg for patients with glomerular filtration rate (GFR) < 30-50. If the calculated GFR drops to 30 mL/min/1.73m2 or below, patients will receive study medication 25mg daily
    Other Name: Januvia
  • Drug: Placebo
    One pill daily until discharge
  • Drug: Regular Human Insulin
    Continuous intravenous insulin given to ICU patients with a BG > 180 mg/DL for two consecutive readings and will be started on Regular Human Insulin adjusted to achieve and maintain a BG target between 110 - 180 mg/dL following standard hospital protocol. Intravenous insulin infusion will be continued until the patient is able to eat and/or transferred to non-ICU service. In previous studies, average length of insulin infusion in patients with stress hyperglycemia was 16.9±19 hours and the amount of IV insulin requirement was 18.6±24.3 U/day.
    Other Name: Novolin-R, Humulin-R
  • Drug: Insulin glargine

    When regular insulin is discontinued, if needed, insulin glargine will be given once daily. Patients who required continuous insulin infusion at an average rate >2U/h will be transitioned to basal (to be given approx. 4 hours prior to discontinuing the insulin drip) starting at a dose 0.2 U/Kg/d.

    Subjects with a BG at 140-200 mg/dL will start glargine at 0.2 U/kg weight per day. And subjects with BG between 201-400 mg/dL will start glargine at 0.2 U/Kg/day

    The basal insulin dose will be adjusted as follow:

    • If fasting and pre-dinner BG is between 100 - 180 mg/dL in the absence of hypoglycemia the previous day: no change
    • If fasting and pre-dinner BG is between 180 - 240 mg/dL in the absence of hypoglycemia: increase glargine by 10% every day
    • If fasting and pre-dinner BG is > 241 mg/dL in the absence of hypoglycemia the previous day: increase glargine dose by 20% every day
    • If fasting and pre-dinner BG is < 100 mg/dL in the absence of hypoglycemia: stop glargine
    Other Name: Lantus (glargine)
  • Drug: Supplemental insulin (Insulin lispro)

    Insulin lispro will be administered before meals in addition to scheduled insulin dose following the supplemental insulin scale protocol. At bedtime, half of supplemental sliding scale insulin starting at BG >240 mg/dL will be given.

    For the subjects receiving supplemental insulin lispro with BG levels greater than 180 mg/dL, then supplemental insulin scale is as follows:

    • BG between 181-220 mg/dL; 2-4 units of insulin lispro
    • BG between 221-260 mg/dL; 3-5 units of insulin lispro
    • BG between 261-300 mg/dL; 4-6 units of insulin lispro
    • BG between 301-350 mg/dL; 5-7 units of insulin lispro
    • BG between 351-400 mg/dL; 6-8 units of insulin lispro
    • BG > 400 mg/dL; 7-9 units of insulin lispro
    Other Name: Humalog
  • Drug: Supplemental insulin (Insulin aspart)

    Insulin aspart will be administered before meals in addition to scheduled insulin dose following the supplemental insulin scale protocol. At bedtime, half of supplemental sliding scale insulin starting at BG >240 mg/dL will be given.

    For the subjects receiving supplemental insulin aspart with BG levels greater than 180 mg/dL, then supplemental insulin scale is as follows:

    • BG between 181-220 mg/dL; 2-4 units of insulin aspart
    • BG between 221-260 mg/dL; 3-5 units of insulin aspart
    • BG between 261-300 mg/dL; 4-6 units of insulin aspart
    • BG between 301-350 mg/dL; 5-7 units of insulin aspart
    • BG between 351-400 mg/dL; 6-8 units of insulin aspart
    • BG > 400 mg/dL; 7-9 units of insulin aspart
    Other Name: Novolog
Study Arms  ICMJE
  • Experimental: Sitagliptin
    Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) will be randomized to take sitagliptin. Subjects with stress hyperglycemia (defined as a BG >180 mg/dL) in the intensive care unit (ICU) will continue to receive sitagliptin and will be started on continuous intravenous insulin (Regular Human Insulin) adjusted to achieve and maintain a BG target between 110 - 180 mg/dL following standard hospital protocol. Additionally, once moved to the regular floors and out of ICU, the subjects can receive insulin glargine, insulin lispro, and/or insulin aspart depending on the blood glucose level.
    Interventions:
    • Drug: Sitagliptin
    • Drug: Regular Human Insulin
    • Drug: Insulin glargine
    • Drug: Supplemental insulin (Insulin lispro)
    • Drug: Supplemental insulin (Insulin aspart)
  • Placebo Comparator: Placebo
    Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) will be randomized to take a placebo. Subjects with stress hyperglycemia (defined as a BG >180 mg/dL) in the intensive care unit (ICU) will continue to receive a placebo and will be started on continuous intravenous insulin (Regular Human Insulin) adjusted to achieve and maintain a BG target between 110 - 180 mg/dL following standard hospital protocol. Additionally, once moved to the regular floors and out of ICU, the subjects can receive insulin glargine, insulin lispro, and/or insulin aspart depending on the blood glucose level.
    Interventions:
    • Drug: Placebo
    • Drug: Regular Human Insulin
    • Drug: Insulin glargine
    • Drug: Supplemental insulin (Insulin lispro)
    • Drug: Supplemental insulin (Insulin aspart)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 31, 2017)
68
Original Estimated Enrollment  ICMJE
 (submitted: May 11, 2015)
50
Actual Study Completion Date  ICMJE December 2016
Actual Primary Completion Date December 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Males or females between the ages of 18 and 80 years undergoing, cardiac surgery
  • No previous history of diabetes
  • No previous history of hyperglycemia

Exclusion Criteria:

  • Patients with hyperglycemia (blood glucose > 125 mg/dL); or glycated hemoglobin (HbA1c) > 6.5%; or previous treatment with oral antidiabetic agents or insulin
  • Severely impaired renal function (serum creatinine ≥3.0 mg/dL or GFR < 30 mL/min) or clinically significant hepatic failure
  • Moribund patients and those at imminent risk of death (brain death or cardiac standstill)
  • Subjects with gastrointestinal (GI) obstruction or adynamic ileus or those expected to require GI suction
  • Patients with clinically relevant pancreatic or gallbladder disease
  • Treatment with oral or injectable corticosteroid
  • Mental condition rendering the subject unable to understand the scope, and consequences of the study
  • Female subjects who are pregnant or breast feeding at time of enrollment into the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02443402
Other Study ID Numbers  ICMJE IRB00080209
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Guillermo Umpierrez, Emory University
Study Sponsor  ICMJE Emory University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Guillermo Umpierrez, MD Emory University
PRS Account Emory University
Verification Date January 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP