Tight Intra-Operative Glucose Control During Coronary Artery Bypass Surgery

This study has been terminated.
(Trial suspended on 26 February, following the publication of a trial with negative results (Ann Intern Med 146(4), 2007). Pending ethics committee re-approval.)
Sponsor:
Information provided by:
Rabin Medical Center
ClinicalTrials.gov Identifier:
NCT00394303
First received: October 31, 2006
Last updated: March 31, 2009
Last verified: June 2007
  Purpose

Blood glucose levels increase in response to stress, infection or other conditions faced by patients in the hospital. This occurs commonly among patients with known diabetes, but also among non-diabetic hospitalized patients. Tight glucose control, the maintenance of blood glucose levels within normal limits (80-120 mg/dl), has been shown to improve patient outcomes in the hospital in several settings, mainly among critically ill patients hospitalized in intensive care units.

We plan to assess the importance of tight glucose control during open-heart surgery. The prevalence of hyperglycemia (elevated blood glucose) during this operation is high. Hyperglycemia may be associated with increased vulnerability to surgical site infections, neurological damage, cardiac and renal injury. Conversely, tight glucose control may be associated with hypoglycemia (pathologically low glucose levels) that may results in neurological injury. We hypothesize that tight glucose control will improve patient outcomes following surgery.


Condition Intervention Phase
Coronary Artery Bypass
Drug: Intraoperative continuous insulin infusion
Other: Control
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Tight Intra-Operative Glucose Control Using Continuous Insulin Infusion During Coronary Artery Bypass Surgery: Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by Rabin Medical Center:

Primary Outcome Measures:
  • 30-day all-cause mortality. [ Time Frame: 30-day ] [ Designated as safety issue: Yes ]
  • Deep or organ/ space (mediastinitis) surgical site infections. [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • Acute renal failure during post-operative ICU stay, defined as: doubling of serum creatinine from baseline; or >50% reduction from baseline glomerular filtration rate; or need for renal replacement therapy. [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
  • Perioperative cerebrovascular event defined as any new, temporary or permanent, focal or global neurological deficit. [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Individual components of the composite primary outcome [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
  • 6-months and long-term survival. [ Time Frame: 6 ans 12 months ] [ Designated as safety issue: Yes ]
  • Other infectious complications during ICU stay including pneumonia and bloodstream infections according to CDC criteria [ Time Frame: ICU stay ] [ Designated as safety issue: No ]
  • Antibiotic use [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Durations of intubation, ICU and hospital stay [ Time Frame: hospital stay ] [ Designated as safety issue: No ]
  • Other post-operative complications occurring during ICU stay, including re-intubation, re-operation [ Time Frame: ICU stay ] [ Designated as safety issue: Yes ]
  • Occurrence of hypoglycemia, defined as blood glucose level of 50mg/ dl or less, during surgery and up to the first glucose measurement in ICU. [ Time Frame: during surgery ] [ Designated as safety issue: Yes ]
  • Occurrence of severe hypokalemia, defined as K<2.5 mEq/l, during surgery [ Time Frame: during surgery ] [ Designated as safety issue: Yes ]
  • Glucose control in ICU, during the first 2 post-operative days [ Time Frame: 2 post-operative days ] [ Designated as safety issue: No ]
  • Neurological status before surgery, at discharge and 3 months following surgery: [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Adverse cardiac events occurring during ICU stay [ Time Frame: ICU stay ] [ Designated as safety issue: Yes ]
  • Re-hospitalizations [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 1400
Study Start Date: February 2007
Estimated Study Completion Date: August 2009
Arms Assigned Interventions
Experimental: 1
Intervention
Drug: Intraoperative continuous insulin infusion
Nomogram specified in appendix
No Intervention: 2
Control
Other: Control
Glucose management according to the discretion of the anesthesiologist aimed to maintain glucose levels <200 mg.dl, reflecting current practice.

Detailed Description:

Current evidence supports intensive glucose control for patients in the intensive care unit post-cardiac surgery. The risk-benefit ratio of tight glucose control using continuous insulin infusion during surgery has not been established. Pros for tight control include the association of hyperglycemia with neurological injury, cardiac ischemia, white blood cell dysfunction and renal failure. The cons include adverse effects, mainly hypoglycemia and hypokalemia. As with any intervention in medicine, tight intra-operative glucose control should be assessed in a randomized controlled trial.

Objectives:to assess whether tight intra-operative tight glucose control using continuous insulin infusion reduces morbidity and mortality following cardiac surgery, defined as the incidence rate of surgical site infections, adverse neurological events, renal failure and 30-day mortality following CABG.

Additional outcomes will include the effect of continuous insulin infusion on longer-term mortality; other infectious complications and antibiotic use during hospitalization; cardiovascular outcomes; the need for re-operations; length of hospital stay; readmission; hypoglycemia and other adverse events.

Design: randomized controlled trial, with blinding of outcome assessors.

Participants: all consecutive patients >18 years undergoing CABG, without or without additional valve or other surgery at Rabin Medical Center; Beilinson campus, providing informed consent.

Exclusion criteria: patients with diabetic ketoacidosis, or hyperosmolar coma.

Intervention: Continuous insulin infusion throughout the operation aimed to maintain normoglycemia using a nomogram

Control: Glucose management according to the discretion of the anesthesiologist (continuous or bolus infusion)

During the early post-operative period (ICU-stay following surgery), all patients will be treated with intensive glucose control targeting glucose levels between 80-110.

  Eligibility

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

Inclusion Criteria:

  • All consecutive patients >18 years undergoing CABG, without or without additional valve or other surgery at Rabin Medical Center; Beilinson campus, providing informed consent.

Exclusion Criteria:

  • Patients with diabetic ketoacidosis, or hyperosmolar coma
  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: NCT00394303

Locations
Israel
Rabin Medical Center, Beilinson Hospital
Petah Tikvah, Israel, 49100
Sponsors and Collaborators
Rabin Medical Center
Investigators
Principal Investigator: Mical Paul, MD Rabin Medical Center
  More Information

No publications provided

Responsible Party: Dr. Mical Paul, Rabin Medical Center, Beilinson Hospital
ClinicalTrials.gov Identifier: NCT00394303     History of Changes
Other Study ID Numbers: 4214
Study First Received: October 31, 2006
Last Updated: March 31, 2009
Health Authority: Israel: Ethics Commission

Keywords provided by Rabin Medical Center:
Open heart surgery
Diabetes mellitus
Hyperglycemia
Surgical site infection
Normoglycemia

Additional relevant MeSH terms:
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014