Sitagliptin in Non-Diabetic Patients Undergoing Cardiac Surgery

NCT02443402 | Completed Phase 4 Results DMC

• 1 other identifier: IRB00080209
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to compare sitagliptin and placebo for the prevention of high blood glucose during surgery.

Conditions

Coronary Artery Disease

Keywords

Non diabetic hyperglycemia

Outcome Measures

Primary Outcomes (2)

• 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.

  Post-Surgery (Up to 4 Days)

• Number of Subjects With Persistent Hyperglycemia

  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)

  Post-Surgery (Up to 10 Days)

Secondary Outcomes (26)

• Need for Continuous Intravenous Insulin (CII) for Treatment of Hyperglycemia

  Post-Surgery (Up to 4 Days)

• Mean Daily Intensive Care Unit (ICU) Blood Glucose (BG) Concentration

  Post-Surgery (Up to 4 Days)

• Mean Amount of Insulin Therapy in the Intensive Care Unit (ICU)

  Post-Surgery (Up to 4 Days)

• Duration of Continuous Intravenous Insulin (CII)

  Post-Intensive Care Unit (ICU) Discharge (Up to 4 Days)

• Mean Units Subcutaneous (SQ) Insulin Required

  Post-Surgery (Up to 10 Days)

Study Arms (2)

Sitagliptin

EXPERIMENTAL

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.

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

Placebo

PLACEBO COMPARATOR

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.

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

Interventions

Sitagliptin DRUG

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

Also known as: Januvia

Sitagliptin

Placebo DRUG

One pill daily until discharge

Placebo

Regular Human Insulin DRUG

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.

Also known as: Novolin-R, Humulin-R

Placebo; Sitagliptin

Insulin glargine DRUG

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

Also known as: Lantus (glargine)

Placebo; Sitagliptin

Supplemental insulin (Insulin lispro) DRUG

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

Also known as: Humalog

Placebo; Sitagliptin

Supplemental insulin (Insulin aspart) DRUG

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

Also known as: Novolog

Placebo; Sitagliptin

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females between the ages of 18 and 80 years undergoing, cardiac surgery
• No previous history of diabetes
• No previous history of hyperglycemia

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead

Study Sites (4)

Grady Health System

Atlanta, Georgia, 30303, United States

Location

Emory University Hospital - Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

Location

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Sitagliptin Phosphate; Insulin; Insulin Glargine; Insulin Lispro; Insulin Aspart

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Insulin, Long-Acting; Insulin, Short-Acting

Results Point of Contact

• Title: Dr. Guillermo Umpierrez
• Organization: Emory University

geumpie@emory.edu

404-778-1665

Study Officials

• Guillermo Umpierrez, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 11, 2015
• First Posted: May 13, 2015
• Study Start: January 1, 2016
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: February 6, 2018
• Results First Posted: February 6, 2018

Record last verified: 2018-01

Locations

US (4)