Sitagliptin in Non-Diabetic Patients Undergoing Cardiac Surgery

Sitagliptin for the Prevention and Treatment of Stress Hyperglycemia in Non-Diabetic Patients Undergoing Cardiac Surgery

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02443402

Acronym

SITACABG NonDM

Enrollment

Registered

2015-05-13

Start date

2016-01-31

Completion date

2016-12-31

Last updated

2018-02-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Coronary Artery Disease

Keywords

Non diabetic hyperglycemia

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.

Interventions

DRUGSitagliptin

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

DRUGPlacebo

One pill daily until discharge

DRUGRegular 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.

DRUGInsulin 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

DRUGSupplemental 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

DRUGSupplemental 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

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

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

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Stress Hyperglycemic Events in the Intensive Care Unit (ICU)	Post-Surgery (Up to 4 Days)	Number of participants who developed stress hyperglycemia (BG \>180 mg/dl) during coronary artery bypass grafting (CABG) or after CABG requiring continuous IV insulin infusion (CII) while in the ICU.
Number of Subjects With Persistent Hyperglycemia	Post-Surgery (Up to 10 Days)	Number of subjects with persistent hyperglycemia (2 consecutive fasting and/or premeal BG \> 180 mg/dL, or with average daily BG \>180 mg/dl) who require insulin glargine (rescue therapy) after discontinuation of continuous intravenous insulin (CII)

Secondary

Measure	Time frame	Description
Mean Amount of Insulin Therapy in the Intensive Care Unit (ICU)	Post-Surgery (Up to 4 Days)	The mean number of insulin infusions given per day (unit/day) while subjects are in the ICU. The more insulin given, the more hyperglycemic events experienced.
Duration of Continuous Intravenous Insulin (CII)	Post-Intensive Care Unit (ICU) Discharge (Up to 4 Days)	Mean number of hours on continuous intravenous insulin (CII) after ICU discharge.
Mean Units Subcutaneous (SQ) Insulin Required	Post-Surgery (Up to 10 Days)	Mean number of supplemental insulin units (lispro or aspart) administered after receiving insulin glargine (SQ insulin).
Mean Blood Glucose (BG) Concentration After Transition From Intensive Care Unit (ICU)	Post-Surgery (Up to 4 Days)	The blood glucose levels will be assessed throughout the day using a glucose meter after transition form the ICU. The normal BG range for someone with diabetes is 80-130 mg/dL.
Total Insulin Therapy in the Intensive Care Unit (ICU)	Post-Surgery (Up to 4 Days)	Total amount of insulin glargine insulin (units) administered in the ICU per day.
Number of Participants With Severe Hyperglycemic Events During Continuous Insulin Infusion (CII)	Post-Surgery (Up to 4 Days)	Number of participants with two consecutive blood glucose concentrations \>180 mg/dL in ICU during CII.
Number of Participants With Hyperglycemia After Transition From Intensive Care Unit (ICU)	Post-Surgery (Up to 10 Days)	Number of participants with blood glucose (BG) \>180 after transition from ICU.
Number of Participants With Hypoglycemia During Intensive Care Unit (ICU) Stay	Post-Surgery (Up to 4 Days)	Number of participants with blood glucose (BG) \<70 during ICU stay.
Number of Participants With Hypoglycemia After Transition From Intensive Care Unit (ICU)	Post-Surgery (Up to 4 Days)	Number of participants with blood glucose (BG) \<70 after transition from ICU.
Number of Participants With Blood Glucose Less Than 40 mg/dl	Duration of Hospitalization (Up to 30 Days)	Number of participants with blood glucose (BG) \<40 throughout the duration of hospitalization.
Hospital Mortality Rate	Post-Surgery (Up to 10 Days)	The total number of subject deaths during hospital stay will be recorded.
Intensive Care Unit (ICU) Mortality Rate	Post-Surgery (Up to 4 Days)	The total number of subject deaths during ICU stay will be recorded.
Need for Continuous Intravenous Insulin (CII) for Treatment of Hyperglycemia	Post-Surgery (Up to 4 Days)	Number of subjects with hyperglycemia (BG \>180 mg/dL) who require CII in the ICU.
Hospital Complication Rate	Duration of Hospitalization (Up to 30 days)	The total number of all complications experienced during hospitalization. Participants may experience more than one complication during hospitalization and these will be included in the hospital complication rate.
Length of Stay: Intensive Care Unit (ICU)	Post-Surgery (Up to 4 Days)	Number of days in the ICU after coronary artery bypass graft surgery (CABG).
Length of Hospital Stay After Study Randomization	Post-Randomization (Up to 9 days)	Number of days in the hospital after a participant is randomized to a study intervention.
Number of Participants Re-admitted to the Hospital Due to Wound Infections	Post-Hospital Discharge (Up to 30 Days)	Number of subjects readmitted to the hospital within 30 days due to wound infection.
Number of Participants Re-admitted to the Hospital Not Due to Wound Infections	Post-Hospital Discharge (Up to 30 Days)	Number of subjects readmitted to the hospital within 30 days for all causes excluding wound infection.
Number of Participants With Emergency Room (ER) Visits	Post-Hospital Discharge (Up to 30 Days)	Number of subjects returning to the ER up to 30 days (all-cause) after hospital discharge.
Number of Participants With Infections Not Requiring Hospital Re-admission	Post-Hospital Discharge (Up to 30 Days)	Number of subjects with infections not requiring hospital re-admission within 30 days after hospital discharge.
Number of Subjects Requiring the Use of Inotropes for Greater Than 24 Hours	Post-Surgery (Up to 2 Days)	The number of subjects requiring the use of inotropes for \>24 hours post CABG.
Number of Subjects Requiring Re-intubation	Post-Surgery (Up to 2 Days)	The number of subjects requiring re-intubation after CABG.
Number of Subjects Requiring Re-intubation Within 24 Hours	Post-Surgery (Up to 24 Hours)	The number of subjects requiring re-intubation with 24 after CABG.
Number of Subject Requiring Surgical Re-Intervention	Post-Surgery (Up to 10 Days)	The number of subjects that require surgical re-intervention due to mediastinal exploration and post-operative hemorrhage.
Number of Participants With Cerebrovascular Events	Post-Hospital Discharge (Up to 10 Days)	Number of participants that experienced permanent stroke and reversible ischemic neurologic deficit events.
Mean Daily Intensive Care Unit (ICU) Blood Glucose (BG) Concentration	Post-Surgery (Up to 4 Days)	The blood glucose levels will be assessed throughout the day using a glucose meter. An average will be calculated. The normal BG range for someone with diabetes is 80-130 mg/dL.

Countries

United States

Participant flow

Recruitment details

Participants were recruited from four academic hospitals including Emory University Hospital, Emory Midtown Hospital, Emory Saint Joseph's, and Grady Memorial Hospital in Atlanta, Georgia between January 2016 and October 2016.

Pre-assignment details

Of the 68 participants consented for study participation, seven did not begin study participation after randomization. One participant was a screen failure prior to randomization. All participants that began a study intervention were included in the baseline analysis.

Participants by arm

Arm	Count
Sitagliptin Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) were randomized to take sitagliptin.	32
Placebo Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) were randomized to take a placebo.	28
Total	60

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Screen Failure	1	2
Overall Study	Withdrawal by Subject	3	1

Baseline characteristics

Characteristic	Sitagliptin	Placebo	Total
Age, Continuous	64 years STANDARD_DEVIATION 11	64 years STANDARD_DEVIATION 9	64 years STANDARD_DEVIATION 9.9
Race/Ethnicity, Customized African American	9 Participants	6 Participants	15 Participants
Race/Ethnicity, Customized Caucasian	20 Participants	20 Participants	40 Participants
Race/Ethnicity, Customized Other	3 Participants	2 Participants	5 Participants
Region of Enrollment United States	32 Participants	28 Participants	60 Participants
Sex: Female, Male Female	8 Participants	5 Participants	13 Participants
Sex: Female, Male Male	24 Participants	23 Participants	47 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 32	0 / 28
other Total, other adverse events	22 / 32	15 / 28
serious Total, serious adverse events	9 / 32	7 / 28

Outcome results

Primary

Number of Participants With Stress Hyperglycemic Events in the Intensive Care Unit (ICU)

Number of participants who developed stress hyperglycemia (BG \>180 mg/dl) during coronary artery bypass grafting (CABG) or after CABG requiring continuous IV insulin infusion (CII) while in the ICU.

Time frame: Post-Surgery (Up to 4 Days)