Sitagliptin for Hyperglycemia in Patients With T2DM Undergoing Cardiac Surgery

NCT ID: NCT02556918

Last Updated: 2019-12-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 202 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2018-11-06

Brief Summary

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).

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.

Conditions

Hyperglycemia

Keywords

Coronary artery bypass graft surgery (CABG); Type 2 Diabetes

Study Design

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

Study Groups

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)

Group Type: EXPERIMENTAL

Sitagliptin

Intervention Type: DRUG

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.

Regular Human Insulin

Intervention Type: DRUG

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.

Insulin glargine

Intervention Type: DRUG

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

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 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

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 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

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)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

One pill daily starting one day prior to surgery until discharge from the hospital.

Regular Human Insulin

Intervention Type: DRUG

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.

Insulin glargine

Intervention Type: DRUG

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

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 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

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 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

Interventions

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.

Intervention Type: DRUG

Placebo

One pill daily starting one day prior to surgery until discharge from the hospital.

Intervention Type: 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.

Intervention Type: 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

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 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

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 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

Intervention Type: DRUG

Other Intervention Names

Januvia; Novolin-R; Humulin-R; Lantus; Humalog; Novolog

Eligibility Criteria

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

• 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, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Guillermo Umpierrez, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Grady Health System

Atlanta, Georgia, United States

Emory Univeristy Hospital Midtown

Atlanta, Georgia, United States

Emory University Hospital

Atlanta, Georgia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00082180

Identifier Type: -

Identifier Source: org_study_id