Sitagliptin in Non-Diabetic Patients Undergoing General Surgery

NCT ID: NCT02741687

Last Updated: 2018-06-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2017-04-30

Brief Summary

The purpose of this study is to compare sitagliptin with a placebo for the prevention of high glucose after general surgery.

Detailed Description

Approximately 30-40% of hospitalized patients will develop stress hyperglycemia (high glucose in response to surgery or illness). High glucose is linked to an increased risk of hospital complications including 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. Recent studies have found that inpatient therapy with oral dipeptidyl peptidase-4 inhibitor (DPP4-I) is an effective alternative to insulin in improving glycemic control with low risk of hypoglycemia in general medicine and surgical patients.

Sitagliptin is an oral medication approved by the Food and Drug Administration (FDA) to treat patients with diabetes. The aim of this study is to determine whether treatment with sitagliptin once daily can prevent the development of stress hyperglycemia during the postoperative period in non-diabetic patients undergoing general surgery.

Conditions

Hyperglycemia

Study Design

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

Study Groups

Sitagliptin Arm

Participants will receive sitagliptin beginning the day prior to surgery and continuing daily during hospitalization (up to 10 days post-surgery).

Point of care (POC) testing will be done four times daily, before meals and at bedtime, or every 6 hours for patients who are not eating (NPO). Patients developing hyperglycemia during or after surgery will be treated with insulin per standard of care.

Patients with fasting and/or premeal blood glucose levels >180 mg/dl will receive supplemental insulin provided on a sliding scale. Patients with two consecutive fasting and/or premeal blood glucose levels >180 mg/dl, or with average daily blood glucose levels >180 mg/dl will be started on rescue therapy with subcutaneous insulin once daily plus correction doses by a sliding scale.

Group Type: EXPERIMENTAL

Sitagliptin

Intervention Type: DRUG

Participants will take 100 mg/day for patients with glomerular filtration rate (GFR) \> 50 and 50 mg/day for GFR 30 - 49, beginning on the day prior to surgery and continuing through hospitalization, up to 10 days.

Supplemental insulin (insulin lispro)

Intervention Type: DRUG

Supplemental 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) >240 mg/dL will be given. If a patient is unable to eat, supplemental insulin will be administered every 6 hours with the lowest number of units for that appropriate BG level.

For subjects receiving supplemental insulin lispro with BG levels greater than 180 mg/dL, the 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

Supplemental 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) >240 mg/dL will be given. If a patient is unable to eat, supplemental insulin will be administered every 6 hours with the lowest number of units for that appropriate BG level.

For subjects receiving supplemental insulin aspart with BG levels greater than 180 mg/dL, the 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

Long acting basal insulin (insulin detemir)

Intervention Type: DRUG

Long acting basal insulin therapy will be provided as needed, and will be given once daily, at the same time of day. Participants with blood glucose (BG) >180 mg/dL= start detemir at 0.2 units per kg weight per day and will follow the following adjustment schedule:

• 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 detemir or glargine dose by 10% every day
• Fasting and pre-meal BG >241 mg/dl: increase detemir or glargine dose by 20% every day
• Fasting and pre-meal BG <100 mg/dl: reduce detemir or glargine by 20% or stop if patient is already on less than 0.1 units/kg of body weight

Long acting basal insulin (insulin glargine)

Intervention Type: DRUG

Long acting basal insulin therapy will be provided as needed, and will be given once daily, at the same time of day. Participants with blood glucose (BG) >180 mg/dL= start detemir at 0.2 units per kg weight per day and will follow the following adjustment schedule:

• 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 detemir or glargine dose by 10% every day
• Fasting and pre-meal BG >241 mg/dl: increase detemir or glargine dose by 20% every day
• Fasting and pre-meal BG <100 mg/dl: reduce detemir or glargine by 20% or stop if patient is already on less than 0.1 units/kg of body weight

Placebo Arm

Participants will receive a placebo tablet beginning the day prior to surgery and continuing daily during hospitalization (up to 10 days post-surgery).

Point of care (POC) testing will be done four times daily, before meals and at bedtime, or every 6 hours for patients who are not eating (NPO). Patients developing hyperglycemia during or after surgery will be treated with insulin per standard of care.

Patients with fasting and/or premeal blood glucose levels >180 mg/dl will receive supplemental insulin provided on a sliding scale. Patients with two consecutive fasting and/or premeal blood glucose levels >180 mg/dl, or with average daily blood glucose levels >180 mg/dl will be started on rescue therapy with subcutaneous insulin once daily plus correction doses by a sliding scale.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will take one pill daily beginning on the day prior to surgery and continuing through hospitalization, up to 10 days.

Supplemental insulin (insulin lispro)

Intervention Type: DRUG

Supplemental 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) >240 mg/dL will be given. If a patient is unable to eat, supplemental insulin will be administered every 6 hours with the lowest number of units for that appropriate BG level.

For subjects receiving supplemental insulin lispro with BG levels greater than 180 mg/dL, the 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

Supplemental 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) >240 mg/dL will be given. If a patient is unable to eat, supplemental insulin will be administered every 6 hours with the lowest number of units for that appropriate BG level.

For subjects receiving supplemental insulin aspart with BG levels greater than 180 mg/dL, the 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

Long acting basal insulin (insulin detemir)

Intervention Type: DRUG

Long acting basal insulin therapy will be provided as needed, and will be given once daily, at the same time of day. Participants with blood glucose (BG) >180 mg/dL= start detemir at 0.2 units per kg weight per day and will follow the following adjustment schedule:

• 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 detemir or glargine dose by 10% every day
• Fasting and pre-meal BG >241 mg/dl: increase detemir or glargine dose by 20% every day
• Fasting and pre-meal BG <100 mg/dl: reduce detemir or glargine by 20% or stop if patient is already on less than 0.1 units/kg of body weight

Long acting basal insulin (insulin glargine)

Intervention Type: DRUG

Long acting basal insulin therapy will be provided as needed, and will be given once daily, at the same time of day. Participants with blood glucose (BG) >180 mg/dL= start detemir at 0.2 units per kg weight per day and will follow the following adjustment schedule:

• 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 detemir or glargine dose by 10% every day
• Fasting and pre-meal BG >241 mg/dl: increase detemir or glargine dose by 20% every day
• Fasting and pre-meal BG <100 mg/dl: reduce detemir or glargine by 20% or stop if patient is already on less than 0.1 units/kg of body weight

Interventions

Sitagliptin

Participants will take 100 mg/day for patients with glomerular filtration rate (GFR) \> 50 and 50 mg/day for GFR 30 - 49, beginning on the day prior to surgery and continuing through hospitalization, up to 10 days.

Intervention Type: DRUG

Placebo

Participants will take one pill daily beginning on the day prior to surgery and continuing through hospitalization, up to 10 days.

Intervention Type: DRUG

Supplemental insulin (insulin lispro)

Supplemental 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) >240 mg/dL will be given. If a patient is unable to eat, supplemental insulin will be administered every 6 hours with the lowest number of units for that appropriate BG level.

For subjects receiving supplemental insulin lispro with BG levels greater than 180 mg/dL, the 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)

Supplemental 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) >240 mg/dL will be given. If a patient is unable to eat, supplemental insulin will be administered every 6 hours with the lowest number of units for that appropriate BG level.

For subjects receiving supplemental insulin aspart with BG levels greater than 180 mg/dL, the 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

Long acting basal insulin (insulin detemir)

Long acting basal insulin therapy will be provided as needed, and will be given once daily, at the same time of day. Participants with blood glucose (BG) >180 mg/dL= start detemir at 0.2 units per kg weight per day and will follow the following adjustment schedule:

• 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 detemir or glargine dose by 10% every day
• Fasting and pre-meal BG >241 mg/dl: increase detemir or glargine dose by 20% every day
• Fasting and pre-meal BG <100 mg/dl: reduce detemir or glargine by 20% or stop if patient is already on less than 0.1 units/kg of body weight

Intervention Type: DRUG

Long acting basal insulin (insulin glargine)

Long acting basal insulin therapy will be provided as needed, and will be given once daily, at the same time of day. Participants with blood glucose (BG) >180 mg/dL= start detemir at 0.2 units per kg weight per day and will follow the following adjustment schedule:

• 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 detemir or glargine dose by 10% every day
• Fasting and pre-meal BG >241 mg/dl: increase detemir or glargine dose by 20% every day
• Fasting and pre-meal BG <100 mg/dl: reduce detemir or glargine by 20% or stop if patient is already on less than 0.1 units/kg of body weight

Intervention Type: DRUG

Other Intervention Names

Januvia; Humalog; NovoLog; Levemir; Lantus

Eligibility Criteria

Inclusion Criteria

• Undergoing non-cardiac surgery
• No previous history of diabetes or hyperglycemia
• Fasting blood glucose level of <126 mg/dl
• Blood glucose <126mg/dl at the time of randomization (could occur at any time of the day)

Exclusion Criteria

• History of hyperglycemia (blood glucose equal to or above 126 mg/dl or HbA1C greater than 6.5%) or previous treatment with oral antidiabetic agents or insulin
• Patients undergoing cardiac surgery
• Patients anticipated to require ICU care following surgery
• Severely impaired renal function (GFR < 30 ml/min) or clinically significant hepatic failure
• Moribund patients and those at imminent risk of death (brain death or cardiac standstill)
• Patients with gastrointestinal obstruction or adynamic ileus or those expected to require gastrointestinal suction
• Patients with clinically relevant pancreatic or gallbladder disease
• Treatment with oral (> 5 mg/day) or injectable corticosteroid
• Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
• Pregnancy or breast-feeding at time of enrollment

• 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

Maya Fayfman

Instructor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Maya Fayfman, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Grady Memorial Hospital

Atlanta, Georgia, United States

Emory University Hospital Midtown

Atlanta, Georgia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00087357

Identifier Type: -

Identifier Source: org_study_id