Hyperglycemia
Conditions
Keywords
stress hyperglycemia, blood glucose
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.
Interventions
DRUGSitagliptin
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.
DRUGPlacebo
Participants will take one pill daily beginning on the day prior to surgery and continuing through hospitalization, up to 10 days.
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 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
DRUGLong 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
DRUGLong 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
Sponsors
Emory University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Stress Hyperglycemia | Up to time of discharge from hospital, an average of 10 days | The number of participants with at least one episode of stress hyperglycemia. Stress hyperglycemia is defined as a blood glucose \> 180 mg/dL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Daily Dose of Insulin for Patients Requiring Supplemental Insulin | Up to time of discharge from hospital, an average of 10 days | 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 | Up to time of discharge from hospital, an average of 10 days | Total length of hospital stay |
| Number of Participants With Hypoglycemic Events | Up to time of discharge from hospital, an average of 10 days | 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 | Up to time of discharge from hospital, an average of 10 days | The number of patients who were transferred to the ICU immediately following surgery or anytime while hospitalized after surgery. |
| Number of Patients Requiring Supplemental, Subcutaneous Insulin | Up to time of discharge from hospital, an average of 10 days | Number of patients requiring subcutaneous insulin, either sliding scale insulin or basal insulin |
| Number of Participants With Hospital Readmissions After Discharge | Up to 40 days (average time of discharge from the hospital plus 30 days) | 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 | Up to 40 days (average time of discharge from the hospital plus 30 days) | 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 | Up to 40 days (average time of discharge from the hospital plus 30 days) | 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. |
| Number of Days in the ICU | Up to time of discharge from hospital, an average of 10 days | The number of days a participant spent in the ICU following surgery, when transfer to the ICU was required. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from Emory University Hospital and Grady Hospital in Atlanta, Georgia between June 2016 and March 2017.
Pre-assignment details
A total of 97 patients consented to be in the study and one participant withdrew prior to randomization. After subsequent failure to meet eligibility criteria (such as surgery being cancelled or postponed) and voluntary participant withdrawals prior to receiving the study medication there were 80 participants who received the study intervention.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received a placebo identical to sitagliptin beginning on the day before surgery and continuing daily during hospitalization (up to 10 days post surgery) | 36 |
| Sitagliptin Participants received sitagliptin beginning on the day before surgery and continuing daily during hospitalization (up to 10 days post surgery) | 44 |
| Total | 80 |
Baseline characteristics
| Characteristic | Total | Placebo | Sitagliptin |
|---|---|---|---|
| Admission blood glucose | 103.6 mg/dl STANDARD_DEVIATION 23.4 | 98.5 mg/dl STANDARD_DEVIATION 20 | 107.6 mg/dl STANDARD_DEVIATION 25.3 |
| Age, Continuous | 48.8 years STANDARD_DEVIATION 13.8 | 45.9 years STANDARD_DEVIATION 14.5 | 51.1 years STANDARD_DEVIATION 12.8 |
| ASA Status ASA status = 1 | 8 Participants | 4 Participants | 4 Participants |
| ASA Status ASA status = 2 | 39 Participants | 17 Participants | 22 Participants |
| ASA Status ASA status = 3 | 22 Participants | 9 Participants | 13 Participants |
| ASA Status Unknown | 11 Participants | 6 Participants | 5 Participants |
| Race/Ethnicity, Customized Race Black | 58 Participants | 26 Participants | 32 Participants |
| Race/Ethnicity, Customized Race Other | 3 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 19 Participants | 8 Participants | 11 Participants |
| Region of Enrollment United States | 80 Participants | 36 Participants | 44 Participants |
| Sex: Female, Male Female | 37 Participants | 18 Participants | 19 Participants |
| Sex: Female, Male Male | 43 Participants | 18 Participants | 25 Participants |
| Surgery type Burn/Wound | 5 Participants | 1 Participants | 4 Participants |
| Surgery type Gastrointestinal | 6 Participants | 3 Participants | 3 Participants |
| Surgery type Genitourinary | 23 Participants | 9 Participants | 14 Participants |
| Surgery type gynecologic | 10 Participants | 7 Participants | 3 Participants |
| Surgery type Neurologic | 9 Participants | 4 Participants | 5 Participants |
| Surgery type Oral maxillofacial surgery | 5 Participants | 4 Participants | 1 Participants |
| Surgery type Orthopedic | 17 Participants | 6 Participants | 11 Participants |
| Surgery type Thoracic | 4 Participants | 2 Participants | 2 Participants |
| Surgery type Vascular | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 44 |
| other Total, other adverse events | 5 / 36 | 8 / 44 |
| serious Total, serious adverse events | 1 / 36 | 1 / 44 |
Outcome results
Primary
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.
Time frame: Up to time of discharge from hospital, an average of 10 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Experiencing Stress Hyperglycemia | 7 Participants |
| Sitagliptin | Number of Participants Experiencing Stress Hyperglycemia | 5 Participants |
Secondary
Length of Hospital Stay
Total length of hospital stay
Time frame: Up to time of discharge from hospital, an average of 10 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Length of Hospital Stay | 9 days |
| Sitagliptin | Length of Hospital Stay | 11 days |
Secondary
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.
Time frame: Up to time of discharge from hospital, an average of 10 days
Population: This analysis includes participants who were transferred to the ICU following surgery.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Number of Days in the ICU | 2.0 days |
| Sitagliptin | Number of Days in the ICU | 1.5 days |
Secondary
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.
Time frame: Up to 40 days (average time of discharge from the hospital plus 30 days)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Experiencing Complications | Respiratory failure | 0 Participants |
| Placebo | Number of Participants Experiencing Complications | Acute kidney injury | 1 Participants |
| Placebo | Number of Participants Experiencing Complications | Wound infection | 0 Participants |
| Placebo | Number of Participants Experiencing Complications | Pneumonia | 0 Participants |
| Placebo | Number of Participants Experiencing Complications | Bacterial septic infection | 0 Participants |
| Placebo | Number of Participants Experiencing Complications | Cardiac event | 0 Participants |
| Sitagliptin | Number of Participants Experiencing Complications | Bacterial septic infection | 0 Participants |
| Sitagliptin | Number of Participants Experiencing Complications | Wound infection | 0 Participants |
| Sitagliptin | Number of Participants Experiencing Complications | Respiratory failure | 0 Participants |
| Sitagliptin | Number of Participants Experiencing Complications | Pneumonia | 0 Participants |
| Sitagliptin | Number of Participants Experiencing Complications | Acute kidney injury | 1 Participants |
| Sitagliptin | Number of Participants Experiencing Complications | Cardiac event | 0 Participants |
Secondary
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.
Time frame: Up to 40 days (average time of discharge from the hospital plus 30 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Emergency Room Visits After Discharge | 0 Participants |
| Sitagliptin | Number of Participants With Emergency Room Visits After Discharge | 0 Participants |
Secondary
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.
Time frame: Up to 40 days (average time of discharge from the hospital plus 30 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Hospital Readmissions After Discharge | 0 Participants |
| Sitagliptin | Number of Participants With Hospital Readmissions After Discharge | 1 Participants |
Secondary
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)
Time frame: Up to time of discharge from hospital, an average of 10 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Hypoglycemic Events | Mild hypoglycemia | 2 Participants |
| Placebo | Number of Participants With Hypoglycemic Events | Clinically significant hypoglycemia | 0 Participants |
| Sitagliptin | Number of Participants With Hypoglycemic Events | Mild hypoglycemia | 5 Participants |
| Sitagliptin | Number of Participants With Hypoglycemic Events | Clinically significant hypoglycemia | 0 Participants |
Secondary
Number of Patients Requiring Supplemental, Subcutaneous Insulin
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Patients Requiring Supplemental, Subcutaneous Insulin | 0 Participants |
| Sitagliptin | Number of Patients Requiring Supplemental, Subcutaneous Insulin | 1 Participants |
Secondary
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.
Time frame: Up to time of discharge from hospital, an average of 10 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Patients Transferred to the ICU Immediately After Surgery or During Hospitalization | 1 Participants |
| Sitagliptin | Number of Patients Transferred to the ICU Immediately After Surgery or During Hospitalization | 2 Participants |
Secondary
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
Time frame: Up to time of discharge from hospital, an average of 10 days
Population: The population for this analysis is limited to participants who received insulin during their hospital stay following surgery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Total Daily Dose of Insulin for Patients Requiring Supplemental Insulin | 5 international units of insulin |