Exenatide for Stress Hyperglycemia

NCT ID: NCT01969149

Last Updated: 2017-10-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

110 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-01-31

Study Completion Date

2016-12-31

Brief Summary

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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.

Detailed Description

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The phase II of the study will assess the safety and the efficacy of a continuous intravenous infusion of exenatide for the management of post operative stress hyperglycemia after planned coronary artery graft bypass (CABG) surgery.

A nested cohort study will concern the 24 first patients included in the study (12 patients/group) to assess the impact of a continuous intravenous infusion of exenatide on post operative glycemic variability after planned CABG surgery.

The aim of the phase III of the study will compare the efficacy of a continuous intravenous infusion of exenatide to the gold standard treatment, i.e the intravenous infusion of short-acting insulin, for the management of post operative stress hyperglycemia after planned CABG surgery.

Conditions

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Stress Hyperglycemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Exenatide

Intervention Type DRUG

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.

Group Type ACTIVE_COMPARATOR

Insulin

Intervention Type DRUG

Interventions

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Exenatide

Intervention Type DRUG

Insulin

Intervention Type DRUG

Other Intervention Names

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Byetta Exendin-4 Incretin Humalog Insulin Lispro Human Analog

Eligibility Criteria

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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.
* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role collaborator

Eli Lilly and Company

INDUSTRY

Sponsor Role collaborator

Centre Hospitalier Universitaire de Besancon

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Guillaume Besch, MD

Role: PRINCIPAL_INVESTIGATOR

CHRU Besançon

Sébastien Pili-Floury, MD, PhD

Role: STUDY_DIRECTOR

CHRU Besançon

Locations

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Post operative intensive care unit of the cardiac surgery department

Besançon, , France

Site Status

Countries

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France

References

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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.

Reference Type BACKGROUND
PMID: 15650975 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20097589 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24247476 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30384842 (View on PubMed)

Other Identifiers

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API/2009/10

Identifier Type: -

Identifier Source: org_study_id