Back to resultsSitagliptin in Non-Diabetic Patients Undergoing General Surgery
Primary Purpose
Hyperglycemia
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Sitagliptin
Placebo
Supplemental insulin (insulin lispro)
Supplemental insulin (insulin aspart)
Long acting basal insulin (insulin detemir)
Long acting basal insulin (insulin glargine)
Sponsored by
About this trial
This is an interventional prevention trial for Hyperglycemia focused on measuring stress hyperglycemia, blood glucose
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
Sites / Locations
- Grady Memorial Hospital
- Emory University Hospital Midtown
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Sitagliptin Arm
Placebo Arm
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Number of Participants Experiencing Stress Hyperglycemia
The number of participants with at least one episode of stress hyperglycemia. Stress hyperglycemia is defined as a blood glucose > 180 mg/dL.
Secondary Outcome Measures
Number of Patients Requiring Supplemental, Subcutaneous Insulin
Number of patients requiring subcutaneous insulin, either sliding scale insulin or basal insulin
Total Daily Dose of Insulin for Patients Requiring Supplemental Insulin
Total daily dose of insulin for patients requiring supplemental insulin during surgery and recovery in participants receiving sitagliptin and those receiving the placebo
Length of Hospital Stay
Total length of hospital stay
Number of Participants With Hypoglycemic Events
Number of participants experiencing at least one episode of mild hypoglycemia (blood glucose < 70 mg/dL) or clinically significant hypoglycemia (blood glucose < 54 mg/dL)
Number of Patients Transferred to the ICU Immediately After Surgery or During Hospitalization
The number of patients who were transferred to the ICU immediately following surgery or anytime while hospitalized after surgery.
Number of Days in the ICU
The number of days a participant spent in the ICU following surgery, when transfer to the ICU was required.
Number of Participants With Hospital Readmissions After Discharge
Readmissions to the study hospital occurring within 30 days of hospital discharge were documented. There were no follow up phone calls or appointments with participants so any hospital readmissions to hospitals other than the one where the surgery occurred are not known.
Number of Participants With Emergency Room Visits After Discharge
Emergency room visits to the study hospital occurring within 30 days of hospital discharge were documented. There were no follow up phone calls or appointments with participants so any emergency room visits to hospitals other than the one where the surgery occurred are not known.
Number of Participants Experiencing Complications
The number of subjects who experience complications including: wound infection, respiratory failure, pneumonia, acute kidney injury with a rise in creatinine by 38 micromoles/Liter from baseline, major adverse cardiac events, bacterial septic infection, and death. Participants will be followed for 30 days following hospital discharge and all complications will be documented.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02741687
Brief Title
Sitagliptin in Non-Diabetic Patients Undergoing General Surgery
Official Title
Prevention of Stress Hyperglycemia With the Use of DPP-4 Inhibitors in Non-diabetic Patients Undergoing Non-cardiac Surgery, a Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
June 2016 (undefined)
Primary Completion Date
April 2017 (Actual)
Study Completion Date
April 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperglycemia
Keywords
stress hyperglycemia, blood glucose
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
80 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sitagliptin Arm
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo Arm
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Sitagliptin
Other Intervention Name(s)
Januvia
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
Participants will take one pill daily beginning on the day prior to surgery and continuing through hospitalization, up to 10 days.
Intervention Type
Drug
Intervention Name(s)
Supplemental insulin (insulin lispro)
Other Intervention Name(s)
Humalog
Intervention Description
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
Intervention Name(s)
Supplemental insulin (insulin aspart)
Other Intervention Name(s)
NovoLog
Intervention Description
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
Intervention Name(s)
Long acting basal insulin (insulin detemir)
Other Intervention Name(s)
Levemir
Intervention Description
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
Intervention Name(s)
Long acting basal insulin (insulin glargine)
Other Intervention Name(s)
Lantus
Intervention Description
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
Primary Outcome Measure Information:
Title
Number of Participants Experiencing Stress Hyperglycemia
Description
The number of participants with at least one episode of stress hyperglycemia. Stress hyperglycemia is defined as a blood glucose > 180 mg/dL.
Time Frame
Up to time of discharge from hospital, an average of 10 days
Secondary Outcome Measure Information:
Title
Number of Patients Requiring Supplemental, Subcutaneous Insulin
Description
Number of patients requiring subcutaneous insulin, either sliding scale insulin or basal insulin
Time Frame
Up to time of discharge from hospital, an average of 10 days
Title
Total Daily Dose of Insulin for Patients Requiring Supplemental Insulin
Description
Total daily dose of insulin for patients requiring supplemental insulin during surgery and recovery in participants receiving sitagliptin and those receiving the placebo
Time Frame
Up to time of discharge from hospital, an average of 10 days
Title
Length of Hospital Stay
Description
Total length of hospital stay
Time Frame
Up to time of discharge from hospital, an average of 10 days
Title
Number of Participants With Hypoglycemic Events
Description
Number of participants experiencing at least one episode of mild hypoglycemia (blood glucose < 70 mg/dL) or clinically significant hypoglycemia (blood glucose < 54 mg/dL)
Time Frame
Up to time of discharge from hospital, an average of 10 days
Title
Number of Patients Transferred to the ICU Immediately After Surgery or During Hospitalization
Description
The number of patients who were transferred to the ICU immediately following surgery or anytime while hospitalized after surgery.
Time Frame
Up to time of discharge from hospital, an average of 10 days
Title
Number of Days in the ICU
Description
The number of days a participant spent in the ICU following surgery, when transfer to the ICU was required.
Time Frame
Up to time of discharge from hospital, an average of 10 days
Title
Number of Participants With Hospital Readmissions After Discharge
Description
Readmissions to the study hospital occurring within 30 days of hospital discharge were documented. There were no follow up phone calls or appointments with participants so any hospital readmissions to hospitals other than the one where the surgery occurred are not known.
Time Frame
Up to 40 days (average time of discharge from the hospital plus 30 days)
Title
Number of Participants With Emergency Room Visits After Discharge
Description
Emergency room visits to the study hospital occurring within 30 days of hospital discharge were documented. There were no follow up phone calls or appointments with participants so any emergency room visits to hospitals other than the one where the surgery occurred are not known.
Time Frame
Up to 40 days (average time of discharge from the hospital plus 30 days)
Title
Number of Participants Experiencing Complications
Description
The number of subjects who experience complications including: wound infection, respiratory failure, pneumonia, acute kidney injury with a rise in creatinine by 38 micromoles/Liter from baseline, major adverse cardiac events, bacterial septic infection, and death. Participants will be followed for 30 days following hospital discharge and all complications will be documented.
Time Frame
Up to 40 days (average time of discharge from the hospital plus 30 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maya Fayfman, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Grady Memorial Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Facility Name
Emory University Hospital Midtown
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Sitagliptin in Non-Diabetic Patients Undergoing General Surgery
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