Normoglycemia and Neurological Outcome
Recruitment status was: Enrolling by invitation
Brain injury patients who meet defined criteria will be assigned to intensive insulin treatment (target blood glucose levels of 10-110 mg/dl) or conventional IV insulin treatment (target glucose of 150-170 mg/dl). Follow up will occur at 3, 6 and 12 months. The primary outcome measure will be neurological outcome at 12 months according to Glasgow Outcome Scale Expanded (GOSE) and Karnofsky Performance Scale (KPS). A general view of outcome will also be presented as favorable (good recovery+ moderate disability), unfavorable (severely disabled+ vegetative state), and dead.
Secondary outcome measures will be length of stay in the intensive care unit and the hospital, the need for ventilatory support or renal replacement therapy, inotropic and vasopressor support, transfusion requirements, and death. Likewise, incidence of seizures and diabetes insipidus will be measured. The investigators will also record systemic complications like pulmonary emboli, pulmonary edema, myocardial infarction, ventricular arrhythmias, and pneumonia.
|Acute, Non-traumatic Subarachnoid Hemorrhage Intraparenchymal Hemorrhage Brain Injuries||Drug: Insulin Drug: Conventional insulin treatment||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||Does Maintenance of Normoglycemia Change Neurological Outcome in Patients Recovering From Traumatic Brain Injury and Subarachnoid or Intraparenchymal Hemorrhage?|
- Glasgow Outcomes Scale Extended score [ Time Frame: 12 months ]The Glasgow Outcome Scale (GOS) is the most widely used measure for traumatic brain injury and other non-traumatic brain injuries and is favored over other measures such as disability rating scale.
- Karnofsky Performance Scale (KPS) [ Time Frame: 12 months ]The Karnofsky Performance Scale (KPS) was originally intended for debilitating diseases such as terminal cancer, but it is currently also used for evaluation of quality of life and long term rehabilitation.
|Study Start Date:||January 2007|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Intensive IV Insulin
Patients will receive IV insulin to maintain target glucose levels of 80-110 mg/dl
All patients in the trial will have blood taken hourly for glucose analysis, regardless of their designated group. Adjustments of the insulin dose will be based on measurements of capillary blood glucose level.
Active Comparator: Conventional IV Insulin
Patents will receive conventional IV insulin treatment with target glucose levels of 150-170 mg/dl
Drug: Conventional insulin treatment
All patients in the trial will have blood taken hourly for glucose analysis , regardless of their designated group. Adjustments of the insulin dose will be based on measurements of capillary blood glucose level.
Demographic data, social and medical histories, and clinical features at onset will be obtained via patient or family interview shortly after admission . We want to get the patients enrolled in our protocol as soon as possible because we believe that hyperglycemia levels greater than 200 mg/dl is a secondary insult that should be prevented as early as possible. However, a twelve-hour period after ICU admission is necessary for initial diagnosis and assessment of the patient's status in order to identify the patient as a potential study subject and to get consent from the patient's legal representative.
Within twelve hours of ICU admission, qualifying patients will be randomized one of the two groups. Randomization will be based on computer-generated codes that will be maintained in sequentially numbered opaque envelopes. The randomization will be stratified according to the severity of neurological injury based on GCS. The three stratification groups will be GCS=6-8, GCS=9-11 and GCS=12-14. Randomization will be done using random sized blocks within stratum, and patients will be randomized within stratum to either:
- Intensive intravenous insulin treatment (Target glucose levels of 80-110 mg/dl)
- Conventional intravenous insulin treatment (Target glucose levels of 150-170 mg/dl)
All patients in the trial will have blood taken hourly for glucose analysis, regardless of their designated group. Adjustments of the insulin dose will be based on measurements of capillary blood glucose level. The interval between the glucose samples will be increased when patients satisfy discharge criteria from the intensive care unit. The insulin dose adjustments will be made by a team of intensive care nurses, assisted by a study nurse who is not otherwise involved in the clinical care of the patients. RBC transfusions, if necessary, will be administered one unit at a time, and the patient's hemoglobin concentration will be measured before and after each transfusion.
All patients enrolled in the study will receive saline infusion supplemented with potassium. An orogastric or nasogastric feeding tube (Dobhoff tube) will be inserted. Enteral feeding will be started per feeding protocol with the goal of starting on day one. After insertion of a nasogastric or orogastric tube, tube position will be verified with abdominal x-ray. Enteral feeding will be instituted with 25 to 30 nonprotein kilocalories per kilogram of body weight per 24 hours and a balanced composition (including 0.13 to 0.26 g of nitrogen per kilogram per 24 hours and 20 to 40 percent of nonprotein in the form of lipids). 69 Formula used will be recorded. Patients will be fed continuously starting at a rate of 25 ml/hour. If continuous enteral feeding cannot be instituted or has to be stopped and enteral nutrition is anticipated to be interrupted for more than 7 days, total parenteral nutrition will be initiated. Patients will be allowed to progress to a regular oral diet after they have passed a swallowing study.
The underlying neurological conditions will be managed by the neurosurgical team according to the protocols of the Department of Neurosurgery of the University of Louisville.
When participating patients' physiological statuses have stabilized and the need for ICU monitoring and care is no longer necessary, they will be discharged to a lower level of care (in accordance with the 1999 guidelines of Task Force of the American College of Critical Care Medicine, Society of Critical Care Medicine). Upon discharge from ICU, patients in all groups will be treated with subcutaneous insulin according to established transition guidelines.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01137773
|United States, Kentucky|
|University of Louisville Hospital|
|Louisville, Kentucky, United States, 40202|
|Principal Investigator:||Rainer Lenhardt, MD||University of Louisville|