Clinical trial NCT01111682: Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure
Official title: Hypertonic Saline vs. Mannitol for Elevated Intercranial Pressure
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Traumatic Brain Injury
Elevated Intracranial Pressure
Keywords: traumatic brain injury
hypertonic saline therapy
intracranial pressure
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2010-04-27
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* 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

Primary outcomes:
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.
timeFrame: 120 hours post initiation of monitoring
Secondary outcomes:
measure: 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.
timeFrame: Daily
measure: Long-term outcomes measured by Disability Rating Scale and Glasgow Outcome Scale-Extended
timeFrame: 3 and 6 months post-injury
measure: Incidence of pre-determined severe adverse events (SAEs): brain hypoxia, delayed decompression, pulmonary edema, renal failure, respiratory complications, seizures, systemic hypoxia, and uncontrollable ICP
timeFrame: Each occurence of an SAE during the patient's hospital stay will be recorded.
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University Hospital
state: Ohio
Study officials:
affiliation: Department of Neurology College of Medicine University of Cincinnati
name: Lori Shutter, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Doyle 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.
citation: Qureshi 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.
citation: Gunnar 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.
citation: Ogden 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.