Normoglycemia and Neurological Outcome

NCT ID: NCT01137773

Last Updated: 2022-01-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2015-12-31

Brief Summary

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 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 blood glucose levels and death.The investigators will also record systemic complications like pulmonary emboli, pulmonary edema, myocardial infarction, ventricular arrhythmias, and pneumonia.

Detailed Description

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:

1. Intensive intravenous insulin treatment (Target glucose levels of 80-110 mg/dl)

2. 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.

Conditions

Acute, Non-traumatic Subarachnoid Hemorrhage; Intraparenchymal Hemorrhage; Brain Injuries

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Intensive IV Insulin

Patients will receive IV insulin to maintain target glucose levels of 80-110 mg/dl

Group Type: EXPERIMENTAL

Insulin

Intervention Type: DRUG

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.

Conventional Insulin Treatment

Patents will receive conventional IV insulin treatment with target glucose levels of 150-170 mg/dl

Group Type: ACTIVE_COMPARATOR

Conventional insulin treatment

Intervention Type: DRUG

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.

Interventions

Insulin

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• non-traumatic SAH, ICH, or TBI
• Glasgow Coma Scale between 6 and 14
• admitted to an ICU of University of Louisville Hospital

Exclusion Criteria

• Patients <18 and >80 years
• GCS Motor score <4 or an overall GCS score of 15
• diabetic patients who suffer from dialysis-dependent diabetic nephropathy
• patients with multiple injuries
• patients who would have been classified as ASA 3 status prior to their acute neurological event

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Louisville

OTHER

Sponsor Role: lead

Responsible Party

Rainer Lenhardt

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rainer Lenhardt, MD

Role: PRINCIPAL_INVESTIGATOR

University of Louisville

Locations

University of Louisville Hospital

Louisville, Kentucky, United States

Countries

United States

Other Identifiers

UofL IRB #562.06

Identifier Type: -

Identifier Source: org_study_id