Sitagliptin for Hyperglycemia in Patients With T2DM Undergoing Cardiac Surgery

NCT02556918 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: IRB00082180
• Study Type: interventional
• Target: 202
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to determine whether treatment with sitagliptin reduces the frequency and severity of high blood sugar (hyperglycemia) after cardiac surgery and to determine whether treatment with sitagliptin is effective in maintaining blood sugar control in patients with type 2 diabetes (T2D).

Conditions

Hyperglycemia

Keywords

Coronary artery bypass graft surgery (CABG); Type 2 Diabetes

Outcome Measures

Primary Outcomes (2)

• Number of Patients With Hyperglycemia in the Intensive Care Unit (ICU)

  Number of patients with blood glucose (BG) levels greater than 180 mg/dl

  2 days (average time of discharge from ICU)

• Number of Patients With Persistent Hyperglycemia

  Number of patients with two consecutive fasting and/or pre-meal blood glucose (BG) greater than 180 mg/dl, or with average daily BG greater than 80 mg/dl who require rescue therapy with subcutaneous (SC) insulin after discontinuation of continuous intravenous insulin infusion (CII).

  10 days (average time of discharge from the hospital)

Secondary Outcomes (24)

• Number of Patients Requiring Continuous Intravenous Insulin Infusion (CII)

  2 days (average time of discharge from ICU)

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

  2 days (average time of discharge from ICU)

• Total IV Insulin in ICU

  2 days (average time of discharge from ICU)

• Mean Insulin Dose Per Day During Intensive Care Unit (ICU) Recovery

  2 days (average time of discharge from ICU)

• Duration of Continuous Intravenous Insulin Infusion (CII)

  Up to 48 hours (average time of discharge from ICU)

Study Arms (2)

Sitagliptin

EXPERIMENTAL

Subjects undergoing cardiac surgery with type 2 diabetes (T2D) will be randomized to receive one tablet of sitagliptin once a day.Subjects with stress hyperglycemia (defined as a blood glucose (BG) greater than 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. Interventions: Drug: Sitagliptin Drug: Regular Human Insulin Drug: Insulin glargine Drug: Supplemental insulin (Insulin lispro) Drug: Supplemental insulin (Insulin aspart)

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 type 2 diabetes will be randomized to receive one tablet of placebo once a day.Subjects with stress hyperglycemia (defined as a blood glucose (BG) greater than 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. Interventions: Drug: Placebo Drug: Regular Human Insulin Drug: Insulin glargine Drug: Supplemental insulin (Insulin lispro) Drug: Supplemental insulin (Insulin aspart)

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 starting one day prior to surgery until discharge from the hospital. Sitagliptin will be dispensed orally at 100 mg/day for patients with a glomeruler filtration rate (GFR) greater than or equal to 50. Patients with a GFR between 30-49 will receive 50 mg/day.

Also known as: Januvia

Sitagliptin

Placebo DRUG

One pill daily starting one day prior to surgery until discharge from the hospital.

Placebo

Regular Human Insulin DRUG

Continuous intravenous insulin given to intensive care unit (ICU) patients with a blood glucose (BG) greater than 180 mg/DL 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 is 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

Patients that required continuous insulin infusion (CII) at a rate \>1U/h will be transitioned to basal insulin (glargine/detemir). Calculate total daily dose (TDD) of insulin from the average CII rate during the last four hours of infusion (example, if the average rate is 2 U/hr., the TDD is 48 U/day) Give 50% of calculated dose as basal (glargine/detemir) insulin every day. Basal insulin will be given approx. 4 hours before discontinuation of CII. The total daily insulin dose will be adjusted as follow: 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 basal dose by 10% every day Fasting and pre-meal BG \>241 mg/dl: increase basal dose by 20% every day Fasting and pre-meal BG \<100 mg/dl: stop basal

Also known as: Lantus

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 blood glucose (BG) greater than 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 greater than 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 blood glucose (BG) greater than 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 greater than 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:

• The ability to provide informed consent
• Ages 18 to 80 years old
• Male or female
• Scheduled to undergo cardiac surgery
• Type 2 Diabetes treated with diet, oral agents,

You may not qualify if:

• Severely impaired kidney function (glomeruler filtration rate (GFR ) less than 30 ml/min)
• Clinically significant liver failure
• Imminent risk of death (brain death or cardiac standstill)
• Gastrointestinal obstruction or adynamic ileus
• Expected to require gastrointestinal suction
• Clinically relevant pancreatic or gallbladder disease
• Using oral or injectable corticosteroid
• Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
• Female subjects are pregnant or breast feeding at time of enrollment into the study

Sponsors & Collaborators

• Emory University: lead

Study Sites (3)

Grady Health System

Atlanta, Georgia, 30303, United States

Location

Emory Univeristy Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Hyperglycemia; Diabetes Mellitus, Type 2

Interventions

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

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Mellitus; Endocrine System 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: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 21, 2015
• First Posted: September 22, 2015
• Study Start: January 1, 2016
• Primary Completion: November 6, 2018
• Study Completion: November 6, 2018
• Last Updated: December 23, 2019
• Results First Posted: December 23, 2019

Record last verified: 2019-12

Locations

US (3)