Exenatide for Stress Hyperglycemia (ExSTRESS)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified October 2013 by Centre Hospitalier Universitaire de Besancon
Sponsor:
Collaborators:
Bristol-Myers Squibb
Eli Lilly and Company
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Besancon
ClinicalTrials.gov Identifier:
NCT01969149
First received: October 15, 2013
Last updated: October 21, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Stress Hyperglycemia
Drug: Exenatide
Drug: Insulin
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Intravenous Exenatide (Byetta®) Versus Insulin for Perioperative Glycemic Control in Cardiac Surgery: the Open-labeled Randomized Phase II/III ExStress Study

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire de Besancon:

Primary Outcome Measures:
  • Percentage of patients spending more than 50 % of the time in the glycemic target range (100 to 140 mg/dl) [ Time Frame: 48 hours ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Hypoglycemia [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]
    Hypoglycemia is defined as blood glucose level less than 80 mg/dl.

  • Severe hypoglycemia [ Time Frame: 48 hours ] [ Designated as safety issue: Yes ]
    Severe hypoglycemia is defined as blood glucose level less than 40 mg/dl.

  • Number of patients needing rescue to insulin therapy protocol [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • Number of adverse events occuring in the exenatide group [ Time Frame: Day 30 ] [ Designated as safety issue: Yes ]
    As the safety of exenatide has never been assessed in the perioperative period in cardiac surgery, all adverse events will be reported, in particular: known adverse events (diarrhea, nausea, vomiting) et severe adverse events (pancreatitis, acute renal failure, death, cardiac arrest).

  • Mortality [ Time Frame: Day 30 ] [ Designated as safety issue: Yes ]
  • Postoperative morbidity [ Time Frame: Day 30 ] [ Designated as safety issue: No ]

    Postoperative morbidity is defined as:

    • neurological complications: stroke.
    • renal complication: acute renal failure requiring dialysis.
    • cardiac complication: cardiogenic shock, arrhythmia, myocardial infarct.
    • vasopressive drug support in postoperative intensive care unit.
    • length of postoperative mechanical ventilation.
    • infectious complication: deep sternal infection.

  • The mean (GluAve) and standard deviation (GluSD) of blood glucose [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • The coefficient of variability (GluCV) of blood glucose level [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    GluCV = GluSD*100/GluAve

  • Mean number of blood glucose measured [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • Mean difference between each blood glucose measurement and 120 mg/dl [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
  • Perioperative cardiac mortality [ Time Frame: Day 30 ] [ Designated as safety issue: No ]
  • Perioperative non cardiac mortality [ Time Frame: Day 30 ] [ Designated as safety issue: No ]
  • Length of stay in intensive care unit [ Time Frame: Day 30 ] [ Designated as safety issue: No ]

Estimated Enrollment: 544
Study Start Date: November 2013
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Exenatide group

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
Other Names:
  • Byetta
  • Exendin-4
  • Incretin
Active Comparator: Insulin group

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
Other Name: Humalog Insulin Lispro Human Analog

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Pregnancy and breast feeding.
  • Pancreatectomy.
  • Acute pancreatitis.
  • Chronic pancreatitis.
  • Type 1 diabetic patients.
  • Insulin requiring type 2 patients.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01969149

Contacts
Contact: Guillaume BESCH, MD gbesch@chu-besancon.fr

Locations
France
Post operative intensive care unit of the cardiac surgery department Not yet recruiting
Besançon, France, 25030
Contact: Guillaume Besch, MD       gbesch@chu-besancon.fr   
Sponsors and Collaborators
Centre Hospitalier Universitaire de Besancon
Bristol-Myers Squibb
Eli Lilly and Company
Investigators
Principal Investigator: Guillaume Besch, MD CHRU Besançon
Study Director: Sébastien Pili-Floury, MD, PhD CHRU Besançon
  More Information

Publications:
Responsible Party: Centre Hospitalier Universitaire de Besancon
ClinicalTrials.gov Identifier: NCT01969149     History of Changes
Other Study ID Numbers: API/2009/10
Study First Received: October 15, 2013
Last Updated: October 21, 2013
Health Authority: France: French Health Authority (ANSM : Agence National de Sécurité du Médicament et des Produits de Santé)

Keywords provided by Centre Hospitalier Universitaire de Besancon:
Stress Hyperglycemia
Perioperative glycemic control
Cardiac surgery
Coronary artery bypass surgery

Additional relevant MeSH terms:
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Exenatide
Insulin LISPRO
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 26, 2014