Exenatide for Stress Hyperglycemia

NCT01969149 | Completed Phase 2 DMC

• 1 other identifier: API/2009/10
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

Stress hyperglycemia is a common phenomenon in cardiac surgery that concerns diabetic and non diabetic patients. It has been shown that perioperative hyperglycemia is an independent risk factor of postoperative mortality and morbidity. The Leuven et al.'s study suggested that strict glycemic perioperative control using an intensive insulin therapy could reduce mortality and morbidity in surgical intensive care's patients. This study included a majority of cardiac surgery patients. Others studies have suggested that the beneficial effect of insulin-based tight perioperative glycemic control might be hampered by iatrogenic hypoglycemia. Moreover, insulin therapy failed to obtain perioperative glycemic stability in most patients. Exenatide (Byetta ®) is an incretin mimetic, characterized by an anti-hyperglycemic effect that depends on the blood glucose level. We hypothesize that continuous intravenous infusion of exenatide could improve perioperative glycemic control and stability and could reduce the risk of iatrogenic hypoglycemia compared to a conventional insulin therapy during the perioperative period of cardiac surgery.

Conditions

Stress Hyperglycemia

Keywords

Stress Hyperglycemia; Perioperative glycemic control; Cardiac surgery; Coronary artery bypass surgery

Outcome Measures

Primary Outcomes (1)

• Percentage of patients spending more than 50 % of the time in the glycemic target range (100 to 140 mg/dl)

  The percentage of time spent achieving blood glucose control is defined as the ratio between the total time spent achieving blood glucose control and the total time under treatment. Blood glucose measurement will be done hourly. Blood glucose control is considered to be achieved between 2 blood glucose measurements if the first blood glucose value measured belongs to blood glucose target interval, defined as blood glucose level between 100 mg/dl l and 140 mg/dl l.

  48 hours

Secondary Outcomes (13)

• Hypoglycemia

  48 hours

• Severe hypoglycemia

  48 hours

• Number of patients needing rescue to insulin therapy protocol

  48 hours

• Number of adverse events occuring in the exenatide group

  Day 30

• Mortality

  Day 30

Study Arms (2)

Exenatide group

EXPERIMENTAL

Exenatide. Exenatide: bolus of 0.05 µg/min infused during the 1st hour of treatment, followed by a continuous infusion of 0.025 µg/min until the end of treatment. The exenatide therapy will begin as soon as a blood glucose level is above 140 mg/dl will be measured. A of exenatide will be intravenously . The treatment will be administrated during the first postoperative 48 hours in the intensive care unit or until intensive care unit discharge if this event occurs earlier.

Drug: Exenatide

Insulin group

ACTIVE COMPARATOR

Insulin: Humalog (insulin lispro human analog). The insulin therapy will begin as soon as a blood glucose level is above 140 mg/dl will be measured. The dose of insulin intravenously infused will be adapted to blood glucose measurements, following the insulin therapy protocol used in our department. The insulin therapy protocol used in our department and prescribed as the benchmark treatment in the present study has been validated in a previous study. It has been derived from the protocol validated by Goldberg et al.

Drug: Insulin

Interventions

Exenatide DRUG

Also known as: Byetta, Exendin-4, Incretin

Exenatide group

Insulin DRUG

Also known as: Humalog Insulin Lispro Human Analog

Insulin group

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age over 18.
• Patient consent.
• Non insulin requiring type 2 diabetic patients.
• Non diabetic patients.
• Planned coronary artery bypass graft (CABG) surgery.
• ASA (American Society of Anesthesiologists) score 1, 2, or 3.

You may not qualify if:

• Pregnancy and breast feeding.
• Pancreatectomy.
• Acute pancreatitis.
• Chronic pancreatitis.
• Type 1 diabetic patients.
• Insulin requiring type 2 patients.
• HbA1c\>8%
• Ketoacidosis.
• Hyperosmolar coma.
• Preoperative blood glucose level above 300 mg/dl \[21\].
• Insulin or exenatide contraindication.
• History of renal transplantation or currently receiving renal dialysis or creatinine clearance below 60 ml/min.
• Emergency surgery.
• Planned non CABG cardiac surgery.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Besancon: lead
• AstraZeneca: collaborator
• Eli Lilly and Company: collaborator

Study Sites (1)

Post operative intensive care unit of the cardiac surgery department

Besançon, 25030, France

Location

Related Publications (4)

• Goldberg PA, Sakharova OV, Barrett PW, Falko LN, Roussel MG, Bak L, Blake-Holmes D, Marieb NJ, Inzucchi SE. Improving glycemic control in the cardiothoracic intensive care unit: clinical experience in two hospital settings. J Cardiothorac Vasc Anesth. 2004 Dec;18(6):690-7. doi: 10.1053/j.jvca.2004.08.003.

  PMID: 15650975 BACKGROUND

• Studer C, Sankou W, Penfornis A, Pili-Floury S, Puyraveau M, Cordier A, Etievent JP, Samain E. Efficacy and safety of an insulin infusion protocol during and after cardiac surgery. Diabetes Metab. 2010 Feb;36(1):71-8. doi: 10.1016/j.diabet.2009.05.008. Epub 2010 Jan 25.

  PMID: 20097589 BACKGROUND

• Galiatsatos P, Gibson BR, Rabiee A, Carlson O, Egan JM, Shannon RP, Andersen DK, Elahi D. The glucoregulatory benefits of glucagon-like peptide-1 (7-36) amide infusion during intensive insulin therapy in critically ill surgical patients: a pilot study. Crit Care Med. 2014 Mar;42(3):638-45. doi: 10.1097/CCM.0000000000000035.

  PMID: 24247476 BACKGROUND

• Besch G, Perrotti A, Salomon du Mont L, Puyraveau M, Ben-Said X, Baltres M, Barrucand B, Flicoteaux G, Vettoretti L, Samain E, Chocron S, Pili-Floury S. Impact of intravenous exenatide infusion for perioperative blood glucose control on myocardial ischemia-reperfusion injuries after coronary artery bypass graft surgery: sub study of the phase II/III ExSTRESS randomized trial. Cardiovasc Diabetol. 2018 Nov 1;17(1):140. doi: 10.1186/s12933-018-0784-y.

  PMID: 30384842 DERIVED

MeSH Terms

Interventions

Exenatide; Incretins; Insulin

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones

Study Officials

• Guillaume Besch, MD

  CHRU Besançon

  PRINCIPAL INVESTIGATOR

• Sébastien Pili-Floury, MD, PhD

  CHRU Besançon

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2013
• First Posted: October 25, 2013
• Study Start: January 1, 2015
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2016
• Last Updated: October 6, 2017

Record last verified: 2016-03

Locations

FR (1)