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The Effects of Corticosteroids, Glucose Control, and Depth-of-Anesthesia on Perioperative Inflammation and Morbidity From Major Non-cardiac Surgery (Dexamethasone, Light Anesthesia and Tight Glucose Control (DeLiT Trial))

This study has been terminated.
(Per interim analysis, for futility.)
Sponsor:
Information provided by (Responsible Party):
d sessler, Cleveland Clinic Foundation
ClinicalTrials.gov Identifier:
NCT00995501
First received: October 14, 2009
Last updated: March 15, 2017
Last verified: March 2017
  Purpose

Evidence thus suggests that steroid administration, tight glucose control, and avoidance of deep anesthesia may decrease perioperative morbidity by reducing the inflammatory response to surgery. Using a three-way factorial approach, the investigators thus propose to test the primary hypotheses that major perioperative morbidity is reduced by: 1) low-dose dexamethasone; 2) intensive perioperative glucose control; and 3) lighter anesthesia.

Secondary hypotheses include that each intervention reduces circulating concentrations of the inflammatory marker CRP, and that there is a correlation between C-reactive protein (CRP) and post-operative complications. Anesthetic sensitivity predicts major and minor complications, and delirium Other secondary hypotheses are that each intervention, reduces minor surgical complications, reduces postoperative nausea and vomiting (PONV), reduces postoperative delirium, speeds hospital discharge, improves quality of life (SF-12v2 Health Survey, Christensen's VAS fatigue score), and reduces all-cause one-year mortality.


Condition Intervention
Inflammation Perioperative Morbidity Drug: Dexamethasone Sodium Sulfate Drug: Insulin Drug: anesthesia management Other: Dexamethasone - placebo Other: Insulin - Placebo Other: Anesthesia management -Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Participant, Investigator
Primary Purpose: Treatment
Official Title: The Effects of Corticosteroids, Glucose Control, and Depth-of-Anesthesia on Perioperative Inflammation and Morbidity From Major Non-cardiac Surgery (Dexamethasone, Light Anesthesia and Tight Glucose Control (DeLiT Trial))

Resource links provided by NLM:


Further study details as provided by d sessler, Cleveland Clinic Foundation:

Primary Outcome Measures:
  • Major Perioperative Morbidity [ Time Frame: 30 day after surgery ]
    Our primary outcome was a collapsed composite endpoint (any versus none) defined as the occurrence of at least one of sixteen major complications before hospital discharge, including sepsis, severe surgical site infection, myocardial infarction, heart failure, stroke, unstable ventricular arrhythmias, pulmonary embolism, pneumonia, respiratory failure, dialysis dependent renal failure, large pleural or peritoneal effusions, major bleeding, major wound and surgical site healing complications, vascular graft thrombosis, and 30-day mortality.


Secondary Outcome Measures:
  • 1 Year Mortality [ Time Frame: 1 year after surgery ]
    All-cause mortality


Enrollment: 381
Study Start Date: January 2007
Study Completion Date: December 2015
Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Intensive Glucose Control, Dexamethasone, light anesthesia
  • Intensive Glucose Control The target range for blood glucose will be 80-110 mg/dl
  • Dexamethasone Dexamethasone administered at 8 mg given 1-2 hours before surgery (incision time), 4 mg on the first postoperative morning, and 2 mg on the second postoperative morning.
  • Light anesthesia target BIS of 55
Drug: Dexamethasone Sodium Sulfate
8 mg given 1-2 hours before surgery (incision time), 4 mg on the first postoperative morning, and 2 mg on the second postoperative morning
Drug: Insulin
Insulin to maintain blood glucose 80-110 mg/dl.
Drug: anesthesia management
Light anesthesia to maintain BIS about 55
Active Comparator: Intensive Glucose Control, Dexamethasone, Deep anesthesia
  • Intensive Glucose Control The target range for blood glucose will be 80-110 mg/dl
  • Dexamethasone Dexamethasone administered at 8 mg given 1-2 hours before surgery (incision time), 4 mg on the first postoperative morning, and 2 mg on the second postoperative morning.
  • Deep anesthesia target BIS of 35
Drug: Dexamethasone Sodium Sulfate
8 mg given 1-2 hours before surgery (incision time), 4 mg on the first postoperative morning, and 2 mg on the second postoperative morning
Drug: Insulin
Insulin to maintain blood glucose 80-110 mg/dl.
Other: Anesthesia management -Placebo
Deep anesthesia to maintain BIS about 35
Active Comparator: Intensive Glucose Control, placebo, Light anesthesia
  • Intensive Glucose Control The target range for blood glucose will be 80-110 mg/dl
  • Placebo Placebo administered at 8 mg given 1-2 hours before surgery (incision time), 4 mg on the first postoperative morning, and 2 mg on the second postoperative morning.
  • Light anesthesia target BIS of 55
Drug: Dexamethasone Sodium Sulfate
8 mg given 1-2 hours before surgery (incision time), 4 mg on the first postoperative morning, and 2 mg on the second postoperative morning
Drug: anesthesia management
Light anesthesia to maintain BIS about 55
Other: Insulin - Placebo
Insulin to maintain blood glucose 180-200 mg/dl.
Active Comparator: Conventional Glucose Control, Dexamethasone, Light anesthesia
  • Conventional Glucose Control The target range for blood glucose will be 180-200 mg/dl
  • Dexamethasone Dexamethasone administered at 8 mg given 1-2 hours before surgery (incision time), 4 mg on the first postoperative morning, and 2 mg on the second postoperative morning.
  • Light anesthesia target BIS of 55
Drug: Insulin
Insulin to maintain blood glucose 80-110 mg/dl.
Drug: anesthesia management
Light anesthesia to maintain BIS about 55
Other: Dexamethasone - placebo
8 mg given 1-2 hours before surgery (incision time), 4 mg on the first postoperative morning, and 2 mg on the second postoperative morning
Active Comparator: Intensive Glucose Control, Placebo, Deep anesthesia
  • Intensive Glucose Control The target range for blood glucose will be 80-110 mg/dl
  • Placebo Placebo administered at 8 mg given 1-2 hours before surgery (incision time), 4 mg on the first postoperative morning, and 2 mg on the second postoperative morning.
  • Deep anesthesia target BIS of 35
Drug: Dexamethasone Sodium Sulfate
8 mg given 1-2 hours before surgery (incision time), 4 mg on the first postoperative morning, and 2 mg on the second postoperative morning
Other: Insulin - Placebo
Insulin to maintain blood glucose 180-200 mg/dl.
Other: Anesthesia management -Placebo
Deep anesthesia to maintain BIS about 35
Active Comparator: Conventional Glucose Control, Dexamethasone, Deep anesthesia
  • Conventional Glucose Control The target range for blood glucose will be 180-200 mg/dl
  • Dexamethasone Dexamethasone administered at 8 mg given 1-2 hours before surgery (incision time), 4 mg on the first postoperative morning, and 2 mg on the second postoperative morning.
  • Deep anesthesia target BIS of 35
Drug: Insulin
Insulin to maintain blood glucose 80-110 mg/dl.
Other: Dexamethasone - placebo
8 mg given 1-2 hours before surgery (incision time), 4 mg on the first postoperative morning, and 2 mg on the second postoperative morning
Other: Anesthesia management -Placebo
Deep anesthesia to maintain BIS about 35
Active Comparator: Conventional Glucose Control, Placebo, Light anesthesia
  • Conventional Glucose Control The target range for blood glucose will be 180-200 mg/dl
  • Placebo Placebo administered at 8 mg given 1-2 hours before surgery (incision time), 4 mg on the first postoperative morning, and 2 mg on the second postoperative morning.
  • Light anesthesia target BIS of 55
Drug: anesthesia management
Light anesthesia to maintain BIS about 55
Other: Dexamethasone - placebo
8 mg given 1-2 hours before surgery (incision time), 4 mg on the first postoperative morning, and 2 mg on the second postoperative morning
Other: Insulin - Placebo
Insulin to maintain blood glucose 180-200 mg/dl.
Placebo Comparator: Conventional Glucose Control, Placebo, Deep anesthesia
  • Conventional Glucose Control The target range for blood glucose will be 180-200 mg/dl
  • Placebo Placebo administered at 8 mg given 1-2 hours before surgery (incision time), 4 mg on the first postoperative morning, and 2 mg on the second postoperative morning.
  • Deep anesthesia target BIS of 35
Other: Dexamethasone - placebo
8 mg given 1-2 hours before surgery (incision time), 4 mg on the first postoperative morning, and 2 mg on the second postoperative morning
Other: Insulin - Placebo
Insulin to maintain blood glucose 180-200 mg/dl.
Other: Anesthesia management -Placebo
Deep anesthesia to maintain BIS about 35

Detailed Description:

The perioperative period is characterized by an intense inflammatory response marked by elevated concentrations of inflammatory markers like C-Reactive Protein (CRP). This response has been linked to increased perioperative morbidity and mortality. Available evidence suggests that blunting the inflammatory response to surgical trauma might improve perioperative outcomes. The putative benefits from blunting the surgical stress response are likely to be greatest in high-risk patients such as those having major non-cardiac surgery. We will study three interventions potentially modulating perioperative inflammation, corticosteroids, tight glucose control and light anesthesia and their effects on major morbidity and mortality resulting from major non-cardiac surgery.

Steroids are the most powerful routinely available anti-inflammatory drugs. They decrease perioperative concentrations of inflammatory markers and improve outcomes after cardiac and abdominal surgery.

Poorly controlled blood glucose worsens the inflammatory response to surgery. Hyperglycemia impairs wound healing, increases infection risk, increases overall hospital mortality, increases the risk of perioperative renal failure, and augments transfusion requirements. Treatment of hyperglycemia has been shown to improve outcomes and decrease mortality in cardiac patients. Also in critically ill patients, it decreased inflammatory markers, overall hospital mortality by 34%, blood stream infections by 46%, and acute renal failure by 41%.

Cumulative deep hypnotic time is associated with increased one-year all-cause mortality, possibly through aggravation of the inflammatory response to surgery. In contrast, avoidance of deep anesthesia appears to reduce postoperative CRP levels, the risk of nausea and vomiting, as well as postoperative hemodynamic, respiratory and infectious complications.

Evidence thus suggests that steroid administration, tight glucose control, and avoidance of deep anesthesia may decrease perioperative morbidity by reducing the inflammatory response to surgery. Using a three-way factorial approach, we thus propose to test the primary hypotheses that major perioperative morbidity is reduced by: 1) low-dose dexamethasone; 2) intensive perioperative glucose control; and, 3) lighter anesthesia.

Secondary hypotheses include that each intervention reduces circulating concentrations of the inflammatory marker CRP, and that there is a correlation between CRP and post-operative complications. Anesthetic sensitivity predicts major and minor complications, and delirium Other secondary hypotheses are that each intervention, reduces minor surgical complications, reduces postoperative nausea and vomiting (PONV), reduces postoperative delirium, speeds hospital discharge, improves quality of life (SF-12v2 Health Survey, Christensen's VAS fatigue score), and reduces all-cause one-year mortality.

  Eligibility

Ages Eligible for Study:   40 Years to 90 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥40 years old.
  2. Major non-cardiac surgical procedures scheduled to take ≥ two hours done under general anesthesia.
  3. Written informed consent

Exclusion Criteria:

  1. Recent intravenous or oral steroid therapy (within 30 days); inhaled steroids are permitted
  2. Any contraindications to the proposed interventions
  3. ASA Physical Status > 4
  4. Non English speaking patients
  5. Procedures done under regional anesthesia
  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: NCT00995501

Locations
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
d sessler
Investigators
Principal Investigator: Basem Abdelmalak, MD The Cleveland Clinic
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: d sessler, MD, Cleveland Clinic Foundation
ClinicalTrials.gov Identifier: NCT00995501     History of Changes
Obsolete Identifiers: NCT00433251
Other Study ID Numbers: 07-010
Study First Received: October 14, 2009
Results First Received: March 15, 2017
Last Updated: March 15, 2017

Keywords provided by d sessler, Cleveland Clinic Foundation:
steroid administration
tight glucose control
light anesthesiReducing inflammatory response to surgical stress
a

Additional relevant MeSH terms:
Inflammation
Pathologic Processes
Anesthetics
Insulin, Globin Zinc
Insulin
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Sodium sulfate
BB 1101
Central Nervous System Depressants
Physiological Effects of Drugs
Hypoglycemic Agents
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cathartics

ClinicalTrials.gov processed this record on June 22, 2017