Sitagliptin for Hyperglycemia in Patients With T2DM Undergoing Cardiac Surgery (SITA-CABGDM)

Sitagliptin for the Prevention and Treatment of Hyperglycemia in Patients With Type 2 Diabetes Undergoing Cardiac Surgery

The purpose of this study is to determine whether treatment with sitagliptin reduces the frequency and severity of high blood sugar (hyperglycemia) after cardiac surgery and to determine whether treatment with sitagliptin is effective in maintaining blood sugar control in patients with type 2 diabetes (T2D).

Study Overview

• Status: Completed
• Conditions: Hyperglycemia
• Intervention / Treatment: Drug: Sitagliptin; Drug: Regular Human Insulin; Drug: Insulin glargine; Drug: Supplemental insulin (Insulin lispro); Drug: Supplemental insulin (Insulin aspart); Drug: Placebo

Detailed Description

The purpose of this study is to determine whether treatment with sitagliptin reduces the frequency and severity of high blood sugar (hyperglycemia) and the need for continuous intravenous insulin infusion (CII) in the intensive care unit (ICU) in patients with type 2 diabetes (T2D) undergoing coronary artery bypass graft (CABG) surgery. In addition, the study seeks to determine whether treatment with sitagliptin is effective in maintaining glycemic control and in preventing the need for subcutaneous (SC) insulin therapy in patients with T2D during the transition from intensive care unit (ICU) to regular floor in cardiac surgery patients with T2D.

• Study Type: Interventional
• Enrollment (Actual): 202
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30303
      • Grady Health System
    • Atlanta, Georgia, United States, 30308
      • Emory Univeristy Hospital Midtown

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The ability to provide informed consent
• Ages 18 to 80 years old
• Male or female
• Scheduled to undergo cardiac surgery
• Type 2 Diabetes treated with diet, oral agents,

Exclusion Criteria:

• Severely impaired kidney function (glomeruler filtration rate (GFR ) less than 30 ml/min)
• Clinically significant liver failure
• Imminent risk of death (brain death or cardiac standstill)
• Gastrointestinal obstruction or adynamic ileus
• Expected to require gastrointestinal suction
• Clinically relevant pancreatic or gallbladder disease
• Using oral or injectable corticosteroid
• Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
• Female subjects are pregnant or breast feeding at time of enrollment into the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sitagliptin; Subjects undergoing cardiac surgery with type 2 diabetes (T2D) will be randomized to receive one tablet of sitagliptin once a day.Subjects with stress hyperglycemia (defined as a blood glucose (BG) greater than 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)	Drug: Sitagliptin; Subjects will take one pill daily starting one day prior to surgery until discharge from the hospital. Sitagliptin will be dispensed orally at 100 mg/day for patients with a glomeruler filtration rate (GFR) greater than or equal to 50. Patients with a GFR between 30-49 will receive 50 mg/day.; Other Names: Januvia; Drug: Regular Human Insulin; Continuous intravenous insulin given to intensive care unit (ICU) patients with a blood glucose (BG) greater than 180 mg/DL 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 is 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 Names: Novolin-R; Humulin-R; Drug: Insulin glargine; Patients that required continuous insulin infusion (CII) at a rate >1U/h will be transitioned to basal insulin (glargine/detemir). Calculate total daily dose (TDD) of insulin from the average CII rate during the last four hours of infusion (example, if the average rate is 2 U/hr., the TDD is 48 U/day) Give 50% of calculated dose as basal (glargine/detemir) insulin every day. Basal insulin will be given approx. 4 hours before discontinuation of CII. The total daily insulin dose will be adjusted as follow: Fasting and pre-meal BG between 100-180 mg/dl without hypoglycemia the previous day: no change Fasting and pre-meal BG between >180-240 mg/dl: increase basal dose by 10% every day Fasting and pre-meal BG >241 mg/dl: increase basal dose by 20% every day Fasting and pre-meal BG <100 mg/dl: stop basal; Other Names: Lantus; 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 blood glucose (BG) greater than 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 greater than 400 mg/dL; 7-9 units of insulin lispro; Other Names: 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 blood glucose (BG) greater than 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 greater than 400 mg/dL; 7-9 units of insulin aspart; Other Names: Novolog
Placebo Comparator: Placebo; Subjects undergoing cardiac surgery with type 2 diabetes will be randomized to receive one tablet of placebo once a day.Subjects with stress hyperglycemia (defined as a blood glucose (BG) greater than 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)	Drug: Regular Human Insulin; Continuous intravenous insulin given to intensive care unit (ICU) patients with a blood glucose (BG) greater than 180 mg/DL 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 is 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 Names: Novolin-R; Humulin-R; Drug: Insulin glargine; Patients that required continuous insulin infusion (CII) at a rate >1U/h will be transitioned to basal insulin (glargine/detemir). Calculate total daily dose (TDD) of insulin from the average CII rate during the last four hours of infusion (example, if the average rate is 2 U/hr., the TDD is 48 U/day) Give 50% of calculated dose as basal (glargine/detemir) insulin every day. Basal insulin will be given approx. 4 hours before discontinuation of CII. The total daily insulin dose will be adjusted as follow: Fasting and pre-meal BG between 100-180 mg/dl without hypoglycemia the previous day: no change Fasting and pre-meal BG between >180-240 mg/dl: increase basal dose by 10% every day Fasting and pre-meal BG >241 mg/dl: increase basal dose by 20% every day Fasting and pre-meal BG <100 mg/dl: stop basal; Other Names: Lantus; 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 blood glucose (BG) greater than 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 greater than 400 mg/dL; 7-9 units of insulin lispro; Other Names: 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 blood glucose (BG) greater than 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 greater than 400 mg/dL; 7-9 units of insulin aspart; Other Names: Novolog; Drug: Placebo; One pill daily starting one day prior to surgery until discharge from the hospital.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Hyperglycemia in the Intensive Care Unit (ICU)	Number of patients with blood glucose (BG) levels greater than 180 mg/dl	2 days (average time of discharge from ICU)
Number of Patients With Persistent Hyperglycemia	Number of patients with two consecutive fasting and/or pre-meal blood glucose (BG) greater than 180 mg/dl, or with average daily BG greater than 80 mg/dl who require rescue therapy with subcutaneous (SC) insulin after discontinuation of continuous intravenous insulin infusion (CII).	10 days (average time of discharge from the hospital)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients Requiring Continuous Intravenous Insulin Infusion (CII)	Number of patients requiring CII to achieve a blood glucose level (BG) target between 150-200 mg/dl	2 days (average time of discharge from ICU)
Mean Blood Glucose (BG) Concentration in the Intensive Care Unit (ICU)	Mean blood glucose (BG) concentration of ICU patients during recovery period.	2 days (average time of discharge from ICU)
Total IV Insulin in ICU	Total IV insulin in ICU during recovery period.	2 days (average time of discharge from ICU)
Mean Insulin Dose Per Day During Intensive Care Unit (ICU) Recovery	Mean insulin infusion dose per day of ICU patients during recovery period.	2 days (average time of discharge from ICU)
Duration of Continuous Intravenous Insulin Infusion (CII)	Total hours of continuous intravenous insulin infusion (CII)	Up to 48 hours (average time of discharge from ICU)
Number of Patients Requiring Subcutaneous (SQ) Insulin After Discontinuation of Continuous Intravenous Insulin Infusion (CII)	Number of patients requiring subcutaneous (SQ) insulin after discontinuation of continuous intravenous insulin infusion (CII)	10 days (average time of discharge from the hospital)
Median Number of Days of Subcutaneous (SC) Insulin After Discontinuation of Continuous Intravenous Insulin Infusion (CII)	Median number of days patients requiring SC insulin after discontinuation of CII	Up to 14 days (time of discharge from the hospital)
Mean Post-operative Blood Glucose (BG) Concentration	Mean post-operative blood glucose (BG) concentration during recovery period.	10 days (average time of discharge from the hospital)
Amount of Subcutaneous (SC) Insulin Taken in Intensive Care Unit (ICU)	Total amount of SC insulin taken by ICU patients during recovery period.	2 days (average time of discharge from ICU)
Amount of Subcutaneous (SC) Insulin in Intensive Care Unit (ICU) 48 Hours	Amount of subcutaneous (SC) insulin in intensive care unit (ICU) 48 hours during recovery period.	48 hours during recovery period
Number of Subjects With Hyperglycemia in Intensive Care Unit (ICU)	Number of subjects with hyperglycemia (blood glucose greater than or equal to 300 mg/dL) in ICU recovery period.	2 days (average time of discharge from ICU)
Number of Subjects With Hyperglycemia (Blood Glucose Greater Than or Equal to 300 mg/dL) in Non-ICU	Number of subjects with hyperglycemia (blood glucose greater than or equal to 300 mg/dL) in non-ICU recovery period.	10 days (average time of discharge from the hospital)
Number of Patients With Hypoglycemic Events in Intensive Care Unit (ICU)	Number of patients with events (blood glucose less than 70 mg/dL) in patients in intensive care unit (ICU).	2 days (average time of discharge from ICU)
Number of Patients With Hypoglycemic Events in Non-intensive Care Unit (ICU)	Number of Patients With hypoglycemic events (blood glucose less than 70 mg/dL) in patients in non-intensive care unit (ICU).	10 days (average time of discharge from the hospital)
Number of Patients With Severe Hypoglycemic Events in Intensive Care Unit (ICU)	Number of Patients With severe hypoglycemia (blood glucose less than 40 mg/dL) in patients in intensive care unit (ICU).	2 days (average time of discharge from ICU)
Number of Patients With Severe Hypoglycemic Events in Non-intensive Care Unit (ICU)	Number of Patients With hypoglycemic events (blood glucose less than 40 mg/dL) in patients in non-intensive care unit (ICU).	10 days (average time of discharge from the hospital)
Composite of Perioperative Complications	Number of perioperative complications including hospital mortality, infection,acute renal failure, and acute mycordial infarction.	10 days (average time of discharge from the hospital)
Duration of Intubation	Duration that patients required to be intubated	10 days (average time of discharge from the hospital)
Length of Intensive Care Unit (ICU) Stay	Total number of days spent in intensive care unit (ICU)	2 days (average time of discharge from ICU)
Total Length of Hospital Stay	Total number of days spent in hospital	10 days (average time of discharge from the hospital)
Number of Intensive Care Unit (ICU) Readmission	Number of re-admissions to intensive care unit during the same hospital course.	10 days (average time of discharge from the hospital)
Number of Cerebrovascular Events	Number of cerebrovascular events including permanent stroke and reversible ischemic neurologic deficit	10 days (average time of discharge from the hospital)
Number of Subjects Readmitted to the Hospital	Number of subjects readmitted to the hospital within 30 days (all-cause).	30 days
Number of Subjects Returning to the ER Within 30 Days	Number of subjects returning to the ER within 30 days (all-cause).	30 days

Collaborators and Investigators

• Sponsor: Emory University

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): November 6, 2018
• Study Completion (Actual): November 6, 2018

Study Registration Dates

• First Submitted: September 21, 2015
• First Submitted That Met QC Criteria: September 21, 2015
• First Posted (Estimate): September 22, 2015

Study Record Updates

• Last Update Posted (Actual): December 23, 2019
• Last Update Submitted That Met QC Criteria: December 20, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Type 2 Diabetes; Coronary artery bypass graft surgery (CABG)
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin Glargine; Insulin Lispro; Sitagliptin Phosphate
• Other Study ID Numbers: IRB00082180

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No