Sitagliptin in Non-Diabetic Patients Undergoing General Surgery

NCT02741687 | Completed Phase 4 Results

• 1 other identifier: IRB00087357
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to compare sitagliptin with a placebo for the prevention of high glucose after general surgery.

Conditions

Hyperglycemia

Keywords

stress hyperglycemia; blood glucose

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to time of discharge from hospital, an average of 10 days

Secondary Outcomes (9)

• Number of Patients Requiring Supplemental, Subcutaneous Insulin

  Up to time of discharge from hospital, an average of 10 days

• Total Daily Dose of Insulin for Patients Requiring Supplemental Insulin

  Up to time of discharge from hospital, an average of 10 days

• Length of Hospital Stay

  Up to time of discharge from hospital, an average of 10 days

• Number of Participants With Hypoglycemic Events

  Up to time of discharge from hospital, an average of 10 days

• 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

Study Arms (2)

Sitagliptin Arm

EXPERIMENTAL

Participants will receive sitagliptin beginning the day prior to surgery and continuing daily during hospitalization (up to 10 days post-surgery). Point of care (POC) testing will be done four times daily, before meals and at bedtime, or every 6 hours for patients who are not eating (NPO). Patients developing hyperglycemia during or after surgery will be treated with insulin per standard of care. Patients with fasting and/or premeal blood glucose levels \>180 mg/dl will receive supplemental insulin provided on a sliding scale. Patients with two consecutive fasting and/or premeal blood glucose levels \>180 mg/dl, or with average daily blood glucose levels \>180 mg/dl will be started on rescue therapy with subcutaneous insulin once daily plus correction doses by a sliding scale.

Drug: Sitagliptin; Drug: Supplemental insulin (insulin lispro); Drug: Supplemental insulin (insulin aspart); Drug: Long acting basal insulin (insulin detemir); Drug: Long acting basal insulin (insulin glargine)

Placebo Arm

PLACEBO COMPARATOR

Participants will receive a placebo tablet beginning the day prior to surgery and continuing daily during hospitalization (up to 10 days post-surgery). Point of care (POC) testing will be done four times daily, before meals and at bedtime, or every 6 hours for patients who are not eating (NPO). Patients developing hyperglycemia during or after surgery will be treated with insulin per standard of care. Patients with fasting and/or premeal blood glucose levels \>180 mg/dl will receive supplemental insulin provided on a sliding scale. Patients with two consecutive fasting and/or premeal blood glucose levels \>180 mg/dl, or with average daily blood glucose levels \>180 mg/dl will be started on rescue therapy with subcutaneous insulin once daily plus correction doses by a sliding scale.

Drug: Placebo; Drug: Supplemental insulin (insulin lispro); Drug: Supplemental insulin (insulin aspart); Drug: Long acting basal insulin (insulin detemir); Drug: Long acting basal insulin (insulin glargine)

Interventions

Sitagliptin DRUG

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.

Also known as: Januvia

Sitagliptin Arm

Placebo DRUG

Participants will take one pill daily beginning on the day prior to surgery and continuing through hospitalization, up to 10 days.

Placebo Arm

Supplemental insulin (insulin lispro) DRUG

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

Also known as: Humalog

Placebo Arm; Sitagliptin Arm

Supplemental insulin (insulin aspart) DRUG

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

Also known as: NovoLog

Placebo Arm; Sitagliptin Arm

Long acting basal insulin (insulin detemir) DRUG

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

Also known as: Levemir

Placebo Arm; Sitagliptin Arm

Long acting basal insulin (insulin glargine) DRUG

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

Also known as: Lantus

Placebo Arm; Sitagliptin Arm

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead

Study Sites (2)

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Hyperglycemia

Interventions

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

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Maya Fayfman, MD
• Organization: Emory University

maya.fayfman@emory.edu

404-778-1664

Study Officials

• Maya Fayfman, 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: Instructor of Medicine

Study Record Dates

• First Submitted: April 13, 2016
• First Posted: April 18, 2016
• Study Start: June 1, 2016
• Primary Completion: April 1, 2017
• Study Completion: April 1, 2017
• Last Updated: June 27, 2018
• Results First Posted: June 27, 2018

Record last verified: 2018-05

Locations

US (2)