Acute, Non-traumatic Subarachnoid HemorrhagePhase 4NCT01137773
Normoglycemia and Neurological Outcome
A Phase 4 study testing Insulin and Conventional insulin treatment in people with Acute, Non-traumatic Subarachnoid Hemorrhage and Intraparenchymal Hemorrhage, run by University of Louisville at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Acute, Non-traumatic Subarachnoid Hemorrhage, Intraparenchymal Hemorrhage, Brain Injuries
- What is being tested?
- Insulin and Conventional insulin treatment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2007to Dec 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- non-traumatic SAH, ICH, or TBI
- Glasgow Coma Scale between 6 and 14
- admitted to an ICU of University of Louisville Hospital
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Louisville Hospital
Louisville, Kentucky, 40202
About this study
Official title: Does Maintenance of Normoglycemia Change Neurological Outcome in Patients Recovering From Traumatic Brain Injury and Subarachnoid or Intraparenchymal Hemorrhage?
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.
Read the 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:
- 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.
- Being tested
- Insulin, Conventional insulin treatment
- Keywords
- SAH (Subarachnoid Hemorrhage), Brain Hemorrhage, Traumatic Brain Injury, SAH, ICH
- Medical subject headings
- Brain Injuries, Subarachnoid Hemorrhage, Intracranial Hemorrhages, Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InsulinDrug
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 treatmentDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Intensive IV Insulin | Experimental | Patients will receive IV insulin to maintain target glucose levels of 80-110 mg/dl Receives: Drug: Insulin |
| Conventional Insulin Treatment | Active comparator | Patents will receive conventional IV insulin treatment with target glucose levels of 150-170 mg/dl Receives: Drug: Conventional insulin treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Karnovsky Performance Status Scale of Functional Impairment
The Karnofsky Performance Scale Index allows patients to be classified as to their functional impairment. It can be used to compare effectiveness of different therapies and to assess the prognosis in individual patients. The lower the Karnofsky score, the worse the survival for most serious illnesses. Patients are assigned a value from 0 to 100 based on the following definitions: Normal no complaints; no evidence of disease - 100. Normal activity with effort; some signs or symptoms of disease - 80. Requires occasional assistance, but is able to care for most of his personal needs - 60. Disabled; requires special care and assistance - 40. Very sick; hospital admission necessary; active supportive treatment necessary- 20. Dead- 0
Measured: 3 months
Secondary outcomes (1)
Blood Glucose Concentration
average blood glucose concentration while the patients received insulin drip
Measured: 24 h
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2010 (estimated)
- Study startJan 2007
- Primary completionDec 2014
- Study completionDec 2015
Why it stopped: Slow enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute, Non-traumatic Subarachnoid HemorrhageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Louisville
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rainer Lenhardt, University of Louisville
- Investigators
- Rainer Lenhardt, MD, Principal investigator, University of Louisville
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01137773
- Sponsor's protocol ID
- UofL IRB #562.06
- Status last verified
- Dec 2021
- First submitted
- 3 Jun 2010
- Last updated
- 4 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Maintenance of Normoglycemia Change Neurological Outcome in Patients Recovering From Traumatic Brain Injury and Subarachnoid or Intraparenchymal Hemorrhage?
- ClinicalTrials.gov ID
- NCT01137773
- Acronym / sponsor ID
- UofL IRB #562.06
- Keywords
- SAH (Subarachnoid Hemorrhage), Brain Hemorrhage, Traumatic Brain Injury, SAH, ICH
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow enrollment
- Enrolment
- 56 participants (actual)
- Lead sponsor
- University of LouisvilleUniversity, hospital or other
- Study start
- Jan 2007
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 4 Jun 2010 (estimated)
- Results
- Posted 10 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intensive IV Insulin | Experimental | Drug: InsulinPatients will receive IV insulin to maintain target glucose levels of 80-110 mg/dl |
| Conventional Insulin Treatment | Active comparator | Drug: Conventional insulin treatmentPatents will receive conventional IV insulin treatment with target glucose levels of 150-170 mg/dl |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- non-traumatic SAH, ICH, or TBI
- Glasgow Coma Scale between 6 and 14
- admitted to an ICU of University of Louisville Hospital
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| InsulinAll 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. | Drug | Intensive IV Insulin |
| Conventional insulin treatmentAll 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. | Drug | Conventional Insulin Treatment |
Primary outcome
Karnovsky Performance Status Scale of Functional Impairment
Time frame: 3 months
The Karnofsky Performance Scale Index allows patients to be classified as to their functional impairment. It can be used to compare effectiveness of different therapies and to assess the prognosis in individual patients. The lower the Karnofsky score, the worse the survival for most serious illnesses. Patients are assigned a value from 0 to 100 based on the following definitions: Normal no complaints; no evidence of disease - 100. Normal activity with effort; some signs or symptoms of disease - 80. Requires occasional assistance, but is able to care for most of his personal needs - 60. Disabled; requires special care and assistance - 40. Very sick; hospital admission necessary; active supportive treatment necessary- 20. Dead- 0
1 secondary outcome
Blood Glucose Concentration
Time frame: 24 h
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Acute, Non-traumatic Subarachnoid Hemorrhage
Not yet recruiting
Non-Invasive Triage for Intracranial Hypertension in Prehospital Care
Intracranial Hypertension, Acute Brain Injury
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rainer Lenhardt, MD principal investigator
University of Louisville
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Insulin and Conventional insulin treatment in people with Acute, Non-traumatic Subarachnoid Hemorrhage and Intraparenchymal Hemorrhage, run by University of Louisville at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Karnovsky Performance Status Scale of Functional Impairment (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jan 2022.