Traumatic Brain InjuryPhase 3NCT01111682
Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure
A Phase 3 study testing Mannitol and Hypertonic Saline in people with Traumatic Brain Injury and Elevated Intracranial Pressure, run by University of Cincinnati at 1 site in United States.
Trial summary
This study examines the role of osmotic agents in controlling brain swelling in brain injured individuals. Two osmotic agents -- mannitol and hypertonic saline -- are in common use, and they will be compared in the context of a randomized clinical trial. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Traumatic Brain Injury, Elevated Intracranial Pressure
- What is being tested?
- Mannitol and Hypertonic Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2010to Nov 2010
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- closed traumatic brain injury
- either (i) GCS score 3-8 (inclusive), or (ii) GCS motor score of 5 or less AND abnormal admission CT scan showing intracranial pathology
- hemodynamically stable with systolic blood pressure greater than 90 mmHg
- at least 1 reactive pupil
- age between 18y and 70y (inclusive)
- INR less than 1.5
Who cannot join
- actively on hypertonic saline or mannitol
- hypernatremia (>145 meq/L)
- anuric or with creatinine greater than or equal to 2.5
- known seizure disorder
- penetrating head trauma
- suspected anoxic events
Show all 9Show fewer
- history of, or CT confirmation of, previous brain injury
- any injury that, in the opinion of the Principal Investigator, has a high likelihood of death with the first 72 hours post-injury
- any treatment, condition, or injury that contraindicates treatment with hypertonic saline
Trial locations and contacts
1 site in 1 country.
About this study
This study examines the role of osmotic agents in controlling brain swelling in brain injured individuals. Two osmotic agents -- mannitol and hypertonic saline -- are in common use, and they will be compared in the context of a randomized clinical trial. The goal is to determine if these agent differ in their ability to control episodes of brain swelling.
Read the detailed description
This single-center, randomized, open label trial will compare (i) 0.9% normal saline infusion and boluses of mannitol (control group) with (ii) 3% hypertonic saline, with intermittent boluses as needed, to treat elevated intracranial pressure (ICP) following severe traumatic brain injury.
Patients will be randomized to one of the two study arms following placement of an ICP monitor. Raised ICP will be defined as an ICP greater than 20 mmHG for 20 minutes or longer. In the event of such an event, the appropriate treatment will be administered.
The primary endpoint will be success in ICP control, operationalized as the proportion of time during which ICP is less than or equal to 20 mmHg during the first 120 hours following initiation of monitoring. Secondary endpoints include therapy intensity level, incidence of pre-determined severe adverse events, and long-term outcomes measured at 3 and 6 months post-injury.
- Being tested
- Mannitol, Hypertonic Saline
- Keywords
- traumatic brain injury, hypertonic saline therapy, intracranial pressure
- Medical subject headings
- Brain Injuries, Traumatic, Intracranial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MannitolDrug
0.9% normal saline infusion and boluses of mannitol
Hypertonic SalineDrug
3% hypertonic saline continuous infusion, with intermittent boluses as needed
| Study group | Role | What they receive |
|---|---|---|
| Mannitol | Active comparator | 0.9% normal saline infusion and boluses of mannitol Receives: Drug: Mannitol |
| Hypertonic Saline | Active comparator | 3% hypertonic saline continuous infusion, with intermittent boluses as needed Receives: Drug: Hypertonic Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of time during which ICP is less than or equal to 20 mmHg during the first 120 hours following initiation of ICP monitoring. In the case where a patient is weaned from infusion, full ICP control will be assumed.
ICP will be recorded continuously and the proportion of time during which ICP is uncontrolled will be calculated. Specifically, this will be measured as any period during which ICP > 20 mmHg for 600 seconds or longer.
Measured: 120 hours post initiation of monitoring
Secondary outcomes (3)
Therapy Intensity Level (TIL), reflecting the amount and duration of therapy required to control ICP. TIL incorporates, among others, variables such as degree of head elevation, level of sedation, volume of CSF drainage, and hypocapnia.
Measured: Daily
Long-term outcomes measured by Disability Rating Scale and Glasgow Outcome Scale-Extended
Measured: 3 and 6 months post-injury
Incidence of pre-determined severe adverse events (SAEs): brain hypoxia, delayed decompression, pulmonary edema, renal failure, respiratory complications, seizures, systemic hypoxia, and uncontrollable ICP
For each patient, we will count the number of SAEs in each category. Total SAEs by category and average number of SAEs per patient will be compared between the two study treatments.
Measured: Each occurence of an SAE during the patient's hospital stay will be recorded.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2010 (estimated)
- Study startApr 2010
- Primary completionNov 2010
- Study completionNov 2010
Why it stopped: A significant reduction in head injuries coupled with more frequent use of crainectomy reduced the number of potential subjects.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Sponsor
- Investigators
- Lori Shutter, MD, Principal investigator, Department of Neurology College of Medicine University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01111682
- Sponsor's protocol ID
- Shutter-2010-01
- Status last verified
- Mar 2013
- First submitted
- 22 Apr 2010
- Last updated
- 5 Mar 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Zornow MH. Hypertonic saline as a safe and efficacious treatment of intracranial hypertension. J Neurosurg Anesthesiol. 1996 Apr;8(2):175-7. doi: 10.1097/00008506-199604000-00021. No abstract available.
PubMed 8829566Doyle JA, Davis DP, Hoyt DB. The use of hypertonic saline in the treatment of traumatic brain injury. J Trauma. 2001 Feb;50(2):367-83. doi: 10.1097/00005373-200102000-00030. No abstract available.
PubMed 11242309Qureshi AI, Suarez JI. Use of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension. Crit Care Med. 2000 Sep;28(9):3301-13. doi: 10.1097/00003246-200009000-00032.
PubMed 11008996Gunnar W, Jonasson O, Merlotti G, Stone J, Barrett J. Head injury and hemorrhagic shock: studies of the blood brain barrier and intracranial pressure after resuscitation with normal saline solution, 3% saline solution, and dextran-40. Surgery. 1988 Apr;103(4):398-407.
PubMed 2451302Ogden AT, Mayer SA, Connolly ES Jr. Hyperosmolar agents in neurosurgical practice: the evolving role of hypertonic saline. Neurosurgery. 2005 Aug;57(2):207-15; discussion 207-15. doi: 10.1227/01.neu.0000166533.79031.d8.
PubMed 16094147
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure
- ClinicalTrials.gov ID
- NCT01111682
- Acronym / sponsor ID
- Shutter-2010-01
- Keywords
- traumatic brain injury, hypertonic saline therapy, intracranial pressure
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: A significant reduction in head injuries coupled with more frequent use of crainectomy reduced the number of potential subjects.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- Apr 2010
- Primary completion
- Nov 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 27 Apr 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study examines the role of osmotic agents in controlling brain swelling in brain injured individuals. Two osmotic agents -- mannitol and hypertonic saline -- are in common use, and they will be compared in the context of a randomized clinical trial. The goal is to determine if these agent differ in their ability to control episodes of brain swelling.
Detailed description
This single-center, randomized, open label trial will compare (i) 0.9% normal saline infusion and boluses of mannitol (control group) with (ii) 3% hypertonic saline, with intermittent boluses as needed, to treat elevated intracranial pressure (ICP) following severe traumatic brain injury.
Patients will be randomized to one of the two study arms following placement of an ICP monitor. Raised ICP will be defined as an ICP greater than 20 mmHG for 20 minutes or longer. In the event of such an event, the appropriate treatment will be administered.
The primary endpoint will be success in ICP control, operationalized as the proportion of time during which ICP is less than or equal to 20 mmHg during the first 120 hours following initiation of monitoring. Secondary endpoints include therapy intensity level, incidence of pre-determined severe adverse events, and long-term outcomes measured at 3 and 6 months post-injury.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mannitol | Active comparator | Drug: Mannitol0.9% normal saline infusion and boluses of mannitol |
| Hypertonic Saline | Active comparator | Drug: Hypertonic Saline3% hypertonic saline continuous infusion, with intermittent boluses as needed |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- closed traumatic brain injury
- either (i) GCS score 3-8 (inclusive), or (ii) GCS motor score of 5 or less AND abnormal admission CT scan showing intracranial pathology
- hemodynamically stable with systolic blood pressure greater than 90 mmHg
- at least 1 reactive pupil
- age between 18y and 70y (inclusive)
Key exclusion criteria (9 listed)
- actively on hypertonic saline or mannitol
- hypernatremia (>145 meq/L)
- anuric or with creatinine greater than or equal to 2.5
- known seizure disorder
- penetrating head trauma
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 |
|---|---|---|
| Mannitol0.9% normal saline infusion and boluses of mannitol | Drug | Mannitol |
| Hypertonic Saline3% hypertonic saline continuous infusion, with intermittent boluses as needed | Drug | Hypertonic Saline |
Primary outcome
Proportion of time during which ICP is less than or equal to 20 mmHg during the first 120 hours following initiation of ICP monitoring. In the case where a patient is weaned from infusion, full ICP control will be assumed.
Time frame: 120 hours post initiation of monitoring
ICP will be recorded continuously and the proportion of time during which ICP is uncontrolled will be calculated. Specifically, this will be measured as any period during which ICP > 20 mmHg for 600 seconds or longer.
3 secondary outcomes
Therapy Intensity Level (TIL), reflecting the amount and duration of therapy required to control ICP. TIL incorporates, among others, variables such as degree of head elevation, level of sedation, volume of CSF drainage, and hypocapnia.
Time frame: Daily
Long-term outcomes measured by Disability Rating Scale and Glasgow Outcome Scale-Extended
Time frame: 3 and 6 months post-injury
Incidence of pre-determined severe adverse events (SAEs): brain hypoxia, delayed decompression, pulmonary edema, renal failure, respiratory complications, seizures, systemic hypoxia, and uncontrollable ICP
Time frame: Each occurence of an SAE during the patient's hospital stay will be recorded.
Results and safety
The study was stopped early (reason given: A significant reduction in head injuries coupled with more frequent use of crainectomy reduced the number of potential subjects.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2013.
- Background: PubMed 8829566Zornow MH. Hypertonic saline as a safe and efficacious treatment of intracranial hypertension. J Neurosurg Anesthesiol. 1996 Apr;8(2):175-7. doi: 10.1097/00008506-199604000-00021. No abstract available.
- Background: PubMed 11242309Doyle JA, Davis DP, Hoyt DB. The use of hypertonic saline in the treatment of traumatic brain injury. J Trauma. 2001 Feb;50(2):367-83. doi: 10.1097/00005373-200102000-00030. No abstract available.
- Background: PubMed 11008996Qureshi AI, Suarez JI. Use of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension. Crit Care Med. 2000 Sep;28(9):3301-13. doi: 10.1097/00003246-200009000-00032.
- Background: PubMed 2451302Gunnar W, Jonasson O, Merlotti G, Stone J, Barrett J. Head injury and hemorrhagic shock: studies of the blood brain barrier and intracranial pressure after resuscitation with normal saline solution, 3% saline solution, and dextran-40. Surgery. 1988 Apr;103(4):398-407.
- Background: PubMed 16094147Ogden AT, Mayer SA, Connolly ES Jr. Hyperosmolar agents in neurosurgical practice: the evolving role of hypertonic saline. Neurosurgery. 2005 Aug;57(2):207-15; discussion 207-15. doi: 10.1227/01.neu.0000166533.79031.d8.
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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.
Lori Shutter, MD principal investigator
Department of Neurology College of Medicine University of Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Mannitol and Hypertonic Saline in people with Traumatic Brain Injury and Elevated Intracranial Pressure, run by University of Cincinnati 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 6 inclusion and 9 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 5 Mar 2013. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: A significant reduction in head injuries coupled with more frequent use of crainectomy reduced the number of potential subjects.). Results are not available in the source record.
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?
Proportion of time during which ICP is less than or equal to 20 mmHg during the first 120 hours following initiation of ICP monitoring. In the case where a patient is weaned from infusion, full ICP control will be assumed. (time frame: 120 hours post initiation of monitoring). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01111682, which also lists 5 linked publications.
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 5 Mar 2013.