Sitagliptin in Non-Diabetic Patients Undergoing Cardiac Surgery

Phase 4

Completed

Conditions: Coronary Artery Disease

Interventions: Drug: Sitagliptin
Drug: Placebo
Drug: Regular Human Insulin
Drug: Insulin glargine
Drug: Supplemental insulin (Insulin lispro)
Drug: Supplemental insulin (Insulin aspart)

Registration Number: NCT02443402

Lead Sponsor: Emory University

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 68

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sitagliptin	Regular Human Insulin	Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) will be randomized to take sitagliptin. Subjects with stress hyperglycemia (defined as a BG \>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.
Sitagliptin	Sitagliptin	Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) will be randomized to take sitagliptin. Subjects with stress hyperglycemia (defined as a BG \>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.
Placebo	Regular Human Insulin	Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) will be randomized to take a placebo. Subjects with stress hyperglycemia (defined as a BG \>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.
Sitagliptin	Supplemental insulin (Insulin lispro)	Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) will be randomized to take sitagliptin. Subjects with stress hyperglycemia (defined as a BG \>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.
Placebo	Supplemental insulin (Insulin lispro)	Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) will be randomized to take a placebo. Subjects with stress hyperglycemia (defined as a BG \>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.
Sitagliptin	Supplemental insulin (Insulin aspart)	Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) will be randomized to take sitagliptin. Subjects with stress hyperglycemia (defined as a BG \>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.
Placebo	Placebo	Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) will be randomized to take a placebo. Subjects with stress hyperglycemia (defined as a BG \>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.
Placebo	Supplemental insulin (Insulin aspart)	Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) will be randomized to take a placebo. Subjects with stress hyperglycemia (defined as a BG \>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.
Sitagliptin	Insulin glargine	Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) will be randomized to take sitagliptin. Subjects with stress hyperglycemia (defined as a BG \>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.
Placebo	Insulin glargine	Subjects undergoing cardiac surgery with no history of diabetes and with normal blood glucose (BG) will be randomized to take a placebo. Subjects with stress hyperglycemia (defined as a BG \>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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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.
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 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.
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.
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).
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).
Intensive Care Unit (ICU) Mortality Rate	Post-Surgery (Up to 4 Days)	The total number of subject deaths during ICU stay will be recorded.
Hospital Mortality Rate	Post-Surgery (Up to 10 Days)	The total number of subject deaths during hospital stay will be recorded.
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 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.
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 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.
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.
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 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.
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.
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.
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.
Number of Subjects Requiring Re-intubation	Post-Surgery (Up to 2 Days)	The number of subjects requiring re-intubation after CABG.
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 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 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 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 Within 24 Hours	Post-Surgery (Up to 24 Hours)	The number of subjects requiring re-intubation with 24 after CABG.

Trial Locations

Locations (4): Emory Saint Joseph's Hospital
🇺🇸
Atlanta, Georgia, United States
Grady Health System
🇺🇸
Atlanta, Georgia, United States
Emory University Hospital - Midtown
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Atlanta, Georgia, United States
Emory University Hospital
🇺🇸
Atlanta, Georgia, United States