Sitagliptin in Non-Diabetic Patients Undergoing Cardiac Surgery

NCT ID: NCT02443402

Last Updated: 2018-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2016-12-31

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.

Conditions

Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Sitagliptin

Intervention Type: DRUG

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

Regular Human Insulin

Intervention Type: DRUG

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.

Insulin glargine

Intervention Type: DRUG

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

Supplemental insulin (Insulin lispro)

Intervention Type: DRUG

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

Supplemental insulin (Insulin aspart)

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

One pill daily until discharge

Regular Human Insulin

Intervention Type: DRUG

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.

Insulin glargine

Intervention Type: DRUG

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

Supplemental insulin (Insulin lispro)

Intervention Type: DRUG

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

Supplemental insulin (Insulin aspart)

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Placebo

One pill daily until discharge

Intervention Type: 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.

Intervention Type: 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

Intervention Type: 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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Januvia; Novolin-R, Humulin-R; Lantus (glargine); Humalog; Novolog

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Guillermo Umpierrez

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Guillermo Umpierrez, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Grady Health System

Atlanta, Georgia, United States

Emory University Hospital - Midtown

Atlanta, Georgia, United States

Emory University Hospital

Atlanta, Georgia, United States

Emory Saint Joseph's Hospital

Atlanta, Georgia, United States

Countries

United States

Other Identifiers

IRB00080209

Identifier Type: -

Identifier Source: org_study_id